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Potential Pharmacotherapeutic Phytochemicals from Zingiberaceae for Cancer Prevention

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Pharmacotherapeutic Botanicals for Cancer Chemoprevention

Abstract

Cancer, one of the most nefarious maladies, is set to affect one in five of the global population soon. Aberrant uncontrolled cell divisions, proliferation and metastasis are hallmarks of cancer. For quite some time now, numerous cancer prevention and treatment strategies have been formulated with a capricious investment of wealth and resources. The state-of-the-art treatment procedures rely on surgeries, radiation therapies, stem cell induction in conjunction with chemotherapy, immunotherapy and hormonal therapeutics. Yet, these combined treatments are not foolproof often leading to secondary health risks, unspecific outcomes and toxicity. Plant extracts have been used to prevent and cure cancerous growth since times immemorial. In the traditional Indian pharmacopoeia, many phytochemical extracts are listed as potent pharmacotherapeutics against cancer. Zingiberaceae, one of the largest monocot families with a centre of diversity in India, is a promising source of many anti-cancerous, anti-proliferative compounds, attributable to its high polyphenol and flavonoid contents. Principal phytochemicals include curcumin, curcumol, kaempferol, zerumbone, apigenin, galangin, 6-gingerol and 8-gingerol. These compounds are reportedly effective against human colorectal, cervical, breast, lung, ovarian, gastric and liver cancers. Interestingly, the modus-operandi of each compound against cancer cells is unique: curcumin and curcumol reportedly induced apoptosis via p53 regulation and accumulation of ROS/oxidative stress or by modulation of MAPK pathway and inhibition of NF-κB; kaempferol inhibited angiogenesis by suppressing ERK-NFκB-cMyc-p21-VEGF pathway, while apigenin modulated signalling pathways that include PI3K/AKT, MAPK/ERK, JAK/STAT, NF-κB and Wnt/β-catenin pathways and zerumbone caused apoptosis by expression of pro-apoptotic proteins like Bax via cytochrome-c dependent caspase activation, simultaneously decreasing levels of anti-apoptotic proteins like Bcl2. These phytochemicals are effective in cancer cell lines resistant to chemotherapeutic drugs like cisplatin and 5-fluorouracil. Plant-based compounds offer flexibility of usage and diversity of action, affording recourse to most of the woes left behind by systematic and commercial chemical drugs. In this context, the present chapter will thoroughly look into the pros and cons of using phytochemicals of Zingiberaceae on various cancer cell lines, delving into their mode of action, potential side effects, discussing how far research has progressed and what the immediate future holds for us.

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Abbreviations

AP 1:

Activator protein 1

cAMP:

Cyclic adenosine monophosphate

COX:

Cyclooxygenase

CREB:

Cyclic AMP response element binding

EGCG:

Epigallocatechin gallate

EGFR:

Epidermal growth factor receptor

ERE:

Oestrogen responsive element

ERK:

Extracellular signal-regulated kinases

FAK:

Focal adhesion kinase

FDA:

Food and Drug Administration

FOXO:

Forkhead box O

FU:

Fluorouracil

GSK:

Glycogen synthase kinase

HDAC:

Histone deacetylases

HIF:

Hypoxia-inducible factor

HNSCC:

Head and neck squamous cell carcinoma

IL:

Interleukin

JAK:

Janus kinase

MAPK:

Mitogen-activated protein kinase

MMP:

Matrix metalloproteinase

mTOR:

Mammalian target of rapamycin

NF κB:

Nuclear factor-κB

NRF:

Nuclear factor erythroid 2-related factor

NSCLC:

Non-small cell lung carcinoma

PARP:

Poly ADP ribose polymerase

PI3K:

Phosphatidylinositol 3-kinase

PTEN:

Phosphatase and tensin homolog gene

ROCK:

Rho-associated protein kinase

ROS:

Reactive Oxygen Species

STAT:

Signal transducer and activator of transcription

TGF:

Transforming growth factor

TNF:

Tumour necrosis factor

uPA:

Urokinase plasminogen activator

VEGF:

Vascular endothelial growth factor

References

  1. Kooti W, Servatyari K, Behzadifar M, Asadi-Samani M, Sadeghi F, Nouri B, Zare Marzouni H (2017) Effective medicinal plant in cancer treatment, part 2: review study. Evid Based Complemenary Alternate 22(4):982–995. https://doi.org/10.1177/2156587217696927

    Article  CAS  Google Scholar 

  2. Kuruppu AI, Paranagama P, Goonasekara C (2019) Medicinal plants commonly used against cancer in traditional medicine formulae in Sri Lanka. Saudi Pharm J. https://doi.org/10.1016/j.jsps.2019.02.004

  3. Wang H, Oo Khor T, Shu L, Su ZY, Fuentes F, Lee JH, Tony Kong AN (2012) Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability. Anti-cancer Agent Med 12(10):1281–1305. https://doi.org/10.2174/187152012803833026

    Article  CAS  Google Scholar 

  4. El-Shami K, Oeffinger KC, Erb NL, Willis A, Bretsch JK, Pratt-Chapman ML, Stein KD (2015) American Cancer Society colorectal cancer survivorship care guidelines. CA Cancer J Clin 65(6):427–455. https://doi.org/10.3322/caac.21286-*/

    Article  Google Scholar 

  5. Jamwal R (2018) Bioavailable curcumin formulations: a review of pharmacokinetic studies in healthy volunteers. J Integr Med 16(6):367–374. https://doi.org/10.1016/j.joim.2018.07.001

    Article  PubMed  Google Scholar 

  6. Nurgali K, Jagoe RT, Abalo R (2018) Editorial: adverse effects of cancer chemotherapy: anything new to improve tolerance and reduce sequelae? Front Pharm 9:245. https://doi.org/10.3389/fphar.2018.00245

    Article  CAS  Google Scholar 

  7. Greenwell M, Rahman PKSM (2015) Medicinal plants: their use in anticancer treatment. Int J Pharm Sci 6(10):4103. https://doi.org/10.13040/IJPSR.0975-8232.6(10).4103-12

    Article  CAS  Google Scholar 

  8. Patwardhan B, Mutalik G, Tillu G (2015) Integrative approaches for health: biomedical research, aayurveda and yoga. Academic, New York

    Google Scholar 

  9. Akhtar MA, Swamy MK (2018) Anticancer plants: natural products and biotechnological implements, vol 2. Springer, Singapore. https://doi.org/10.1007/978-981-10-8064-7

    Book  Google Scholar 

  10. Kocyigit A, Guler EM, Dikilitas M (2017) Role of antioxidant phytochemicals in prevention, formation and treatment of cancer. Reac Oxy Sps (ROS) Liv Cells. https://doi.org/10.5772/intechopen.72217

  11. Scarpa ES, Ninfali P (2015) Phytochemicals as innovative therapeutic tools against cancer stem cells. Int J Mol 16(7):15727–15742. https://doi.org/10.3390/ijms160715727

    Article  CAS  Google Scholar 

  12. Kaur V, Kumar M, Kumar A, Kaur K, Dhillon VS, Kaur S (2018) Pharmacotherapeutic potential of phytochemicals: Implications in cancer chemoprevention and future perspectives. Biomed Pharmacol Ther 97:564–586. https://doi.org/10.1016/j.biopha.2017.10.124

    Article  CAS  Google Scholar 

  13. Amararathna M, Johnston MR, Rupasinghe HP (2016) Plant polyphenols as chemopreventive agents for lung cancer. Int J Mol 17(8):1352. https://doi.org/10.3390/ijms17081352

    Article  CAS  Google Scholar 

  14. Dutt R, Garg V, Khatri N, Madan AK (2019) Phytochemicals in anticancer drug development. Anti-cancer Agent Med 19(2):172–183

    CAS  Google Scholar 

  15. Kingston DG (1993) Taxol, an exciting anticancer drug from Taxus brevifolia: an overview. Human medicinal agents from plants. ACS Symp Ser 534(10):138–148. https://doi.org/10.1021/bk-1993-0534.ch010

    Article  CAS  Google Scholar 

  16. Nakamura H, Jun F, Maeda H (2015) Development of next-generation macromolecular drugs based on the EPR effect: challenges and pitfalls. Expert Opin Drug Deliv 12(1):53–64. https://doi.org/10.1517/17425247.2014.955011

    Article  PubMed  CAS  Google Scholar 

  17. Lee KW, Ching SM, Hoo FK, Ramachandran V, Swamy MK (2018) Traditional medicinal plants and their therapeutic potential against major cancer types. In: Anticancer plants: natural products and biotechnological implements. Springer, Singapore, pp 383–410. https://doi.org/10.1007/978-981-10-8064-7_16

    Chapter  Google Scholar 

  18. Dai L, Wang G, Pan W (2017) Andrographolide inhibits proliferation and metastasis of SGC7901 gastric cancer cells. Biomed Res Int 2017:10

    Google Scholar 

  19. Smilkov K, Ackova DG, Cvetkovski A, Ruskovska T, Vidovic B, Atalay M (2019) Piperine: old spice and new nutraceutical? Curr Phar 25(15):1729–1739

    CAS  Google Scholar 

  20. Honari M, Shafabakhsh R, Reiter RJ, Mirzaei H, Asemi Z (2019) Resveratrol is a promising agent for colorectal cancer prevention and treatment: focus on molecular mechanisms. Cancer Cell Int 19(1):180

    PubMed  PubMed Central  Google Scholar 

  21. Jamshidi-Kia F, Lorigooini Z, Amini-Khoei H (2018) Medicinal plants: past history and future perspective. J Herbmed Pharmacol 7(1):1–7

    Google Scholar 

  22. Lichota A, Gwozdzinski K (2018) Anticancer activity of natural compounds from plant and marine environment. Int J Mol 19(11):3533. https://doi.org/10.3390/ijms19113533

    Article  CAS  Google Scholar 

  23. Kress WJ (1990) The phylogeny and classification of the Zingiberales. Ann Missouri Bot 77:698–721. https://doi.org/10.2307/2399669

    Article  Google Scholar 

  24. Kress WJ, Prince LM, Williams KJ (2002) The phylogeny and a new classification of the gingers (Zingiberaceae): evidence from molecular data. Am J Bot 89(10):1682–1696. https://doi.org/10.3732/ajb.89.10.1682

    Article  PubMed  CAS  Google Scholar 

  25. Sabu M (2006) Zingiberaceae and Costaceae of South India. Indian Association of Angiosperm Taxonomy, Kerala

    Google Scholar 

  26. Barbosa GB, Jayasinghe NS, Natera SH, Inutan ED, Peteros NP, Roessner U (2017) From common to rare zingiberaceae plants-a metabolomics study using GC-MS. Phytochemistry 140:141–150

    PubMed  CAS  Google Scholar 

  27. Ghasemzadeh A, Jaafar HZ, Rahmat A (2011) Effects of solvent type on phenolics and flavonoids content and antioxidant activities in two varieties of young ginger (Zingiber officinale Roscoe) extracts. J Med Plant Res 5(7):1147–1154

    CAS  Google Scholar 

  28. Quideau S, Deffieux D, Douat-Casassus C, Pouysegu L (2011) Plant polyphenols: chemical properties, biological activities, and synthesis. Angew Chem Int Ed 50(3):586–621

    CAS  Google Scholar 

  29. Russo GL, Tedesco I, Spagnuolo C, Russo M (2017) Antioxidant polyphenols in cancer treatment: friend, foe or foil? In: Semin Cancer Biol, vol 46. Academic, New York, pp 1–13

    Google Scholar 

  30. Yoon JH, Baek SJ (2005) Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J 46(5):585–596

    PubMed  PubMed Central  CAS  Google Scholar 

  31. Hasimun P, Adnyana IK (2019) Zingiberaceae family effects on alpha-glucosidase activity: implication for diabetes. In: Bioactive food as dietary interventions for diabetes. Academic, New York, pp 387–393

    Google Scholar 

  32. Wal P, Saraswat N, Pal RS, Wal A, Dubey S (2019) A detailed review on traditionally used and potent sources showing anti-pyretic action. RJPT 12(10):5107–5112

    Google Scholar 

  33. Rodríguez-Pérez C, Segura-Carretero A, Del Mar CM (2019) Phenolic compounds as natural and multifunctional anti-obesity agents: a review. Crit Rev Food Sci Nutr 59(8):1212–1229

    PubMed  Google Scholar 

  34. Sunilson JAJ, Suraj R, Rejitha G, Anandarajagopal K, Kumari AVAG, Promwichit P (2009) In vitro antimicrobial evaluation of Zingiber officinale, Curcuma longa and Alpinia galanga extracts as natural food preservatives. Am J Food Technol 4(5):192–200

    Google Scholar 

  35. Danciu C, Vlaia L, Fetea F, Hancianu M, Coricovac DE, Ciurlea SA, Trandafirescu C (2015) Evaluation of phenolic profile, antioxidant and anticancer potential of two main representants of zingiberaceae family against B164A5 murine melanoma cells. Biol Res 48(1):1–9

    PubMed  PubMed Central  Google Scholar 

  36. Basri AM, Taha H, Ahmad N (2017) A review on the pharmacological activities and phytochemicals of Alpinia officinarum (Galangal) extracts derived from bioassay-guided fractionation and isolation. Phcog Rev 11(21):43–56

    PubMed  CAS  Google Scholar 

  37. Chanda S, Ramachandra TV (2019) Phytochemical and pharmacological importance of turmeric (Curcuma longa): a review. RRJoP 9(1):16–23

    CAS  Google Scholar 

  38. Sharifi-Rad M, Varoni EM, Salehi B, Sharifi-Rad J, Matthews KR, Ayatollahi SA, Sharifi-Rad M, Rigano D (2017) Plants of the Genus Zingiber as source of antimicrobial agents: from tradition to pharmacy. Molecules 22(2145):1–20

    Google Scholar 

  39. Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK (2007) Curcumin–phospholipid complex: preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm 330(1-2):155–163. https://doi.org/10.1016/j.ijpharm.2006.09.025

    Article  PubMed  CAS  Google Scholar 

  40. Priyadarsini K (2014) The chemistry of curcumin: from extraction to therapeutic agent. Molecules 19(12):20091–20112. https://doi.org/10.3390/molecules191220091

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Chempakam B, Parthasarathy VA (2006) Turmeric. In: Parthasarathy VA, Chempakam B, Zachariah TJ (eds) Chemistry of spice. CABI, Cambridge, pp 97–123

    Google Scholar 

  42. Jayaprakasha GK, Rao LJ, Sakariah KK (2006) Antioxidant activities of curcumin, demethoxycurcumin and bisdemethoxycurcumin. Food Chem 98(4):720–724. https://doi.org/10.1016/j.foodchem.2005.06.037

    Article  CAS  Google Scholar 

  43. Dairam A, Limson JL, Watkins GM, Antunes E, Daya S (2007) Curcuminoids, curcumin, and demethoxycurcumin reduce lead-induced memory deficits in male Wistar rats. J Agric Food Chem 55(3):1039–1044. https://doi.org/10.1021/jf063446t

    Article  PubMed  CAS  Google Scholar 

  44. Pfeiffer E, Höhle S, Solyom AM, Metzler M (2003) Studies on the stability of turmeric constituents. J Food Eng 56(2-3):257–259. https://doi.org/10.1016/S0260-8774(02)00264-9

    Article  Google Scholar 

  45. Benguedouar L, Lahouel M, Gangloff SC, Durlach A, Grange F, Bernard P, Antonicelli F (2016) Ethanolic extract of algerian propolis and galangin decreased murine melanoma tumor progression in mice. Anti Cancer Agents Med Chem 16(9):1172–1183. https://doi.org/10.2174/1871520616666160211124459

    Article  CAS  Google Scholar 

  46. He X, Wei Z, Wang J, Kou J, Liu W, Fu Y, Yang Z (2016) Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis. Sci Rep 6:28370. https://doi.org/10.1038/srep28370

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Dugasani S, Pichika MR, Nadarajah VD, Balijepalli MK, Tandra S, Korlakunta JN (2010) Comparative antioxidant and anti-inflammatory effects of [6]-gingerol,[8]-gingerol,[10]-gingerol and [6]-shogaol. J Ethnopharmacol 127(2):515–520

    PubMed  CAS  Google Scholar 

  48. Haque MA, Jantan I, Arshad L, Bukhari SNA (2017) Exploring the immunomodulatory and anticancer properties of zerumbone. Food Funct 8(10):3410–3431. https://doi.org/10.1039/C7FO00595D

    Article  PubMed  CAS  Google Scholar 

  49. Antonious GF, Kochhar TS (2003) Zingiberene and curcumene in wild tomato. J Environ Sci Health B 38(4):489–500

    PubMed  Google Scholar 

  50. Swindell WR, Bojanowski K, Chaudhuri RK (2019) A zingerone analog, acetyl zingerone, bolsters matrisome synthesis, inhibits matrix metallopeptidases, and represses IL-17A target gene expression. JID. https://doi.org/10.1016/j.jid.2019.07.715

  51. Chen AY, Chen YC (2013) A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food Chem 138(4):2099–2107. https://doi.org/10.1016/j.foodchem.2012.11.139

    Article  PubMed  CAS  Google Scholar 

  52. Gonçalves LM, Valente IM, Rodrigues JA (2014) An overview on cardamonin. J Med Food 17(6):633–640. https://doi.org/10.1089/jmf.2013.0061

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Ke CS, Liu HS, Yen CH, Huang GC, Cheng HC, Huang CYF, Su CL (2014) Curcumin-induced Aurora-A suppression not only causes mitotic defect and cell cycle arrest but also alters chemosensitivity to anticancer drugs. J Nutr Biochem 25(5):526–539. https://doi.org/10.1016/j.jnutbio.2014.01.003

    Article  PubMed  CAS  Google Scholar 

  54. Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23(1/A):363–398

    PubMed  CAS  Google Scholar 

  55. Nagaraju GP, Aliya S, Zafar SF, Basha R, Diaz R, El-Rayes BF (2012) The impact of curcumin on breast cancer. Integr Biol 4:996–1007. https://doi.org/10.1039/c2ib20088k

    Article  CAS  Google Scholar 

  56. Surh YJ, Han SS, Keum YS, Seo HJ, Lee SS (2000) Inhibitory effects of curcumin and capsaicin on phorbol ester-induced activation of eukaryotic transcription factors, NF-kappaB and AP-1. Biofactors 12(1–4):107–112

    PubMed  CAS  Google Scholar 

  57. Vallianou NG, Evangelopoulos A, Schizas N, Kazazis C (2015) Potential anticancer properties and mechanisms of action of curcumin. Anticancer Res 35(2):645–651

    PubMed  CAS  Google Scholar 

  58. Wilken R, Veena MS, Wang MB, Srivatsan ES (2011) Curcumin: a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer 10(1):12

    PubMed  PubMed Central  CAS  Google Scholar 

  59. Das L, Vinayak M (2015) Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer. PLoS ONE 10:e0124000. https://doi.org/10.1371/journal.pone.0124000

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Sun SQ, Zhang W, Guo Y, Li Z, Chen X, Wang Y, Zhao G (2016) Curcumin inhibits cell growth and induces cell apoptosis through upregulation of miR-33b in gastric cancer. Tumour Biol 37(10):13177–13184. https://doi.org/10.1007/s13277-016-5221-9

    Article  PubMed  CAS  Google Scholar 

  61. Gao SM, Yang JJ, Chen CQ, Chen JJ, Ye LP, Wang LY (2012) Pure curcumin decreases the expression of WT1 by upregulation of miR-15a and miR-16-1 in leukemic cells. J Exp Clin Cancer Res 31(1):27. https://doi.org/10.1186/1756-9966-31-27

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Sa G, Das T (2008) Anti cancer effects of curcumin: cycle of life and death. Cell Div 3(1):14

    PubMed  PubMed Central  Google Scholar 

  63. Sovak MA, Bellas RE, Kim DW, Zanieski GJ, Rogers AE, Traish AM et al (1997) Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer. J Clin Invest 100:2952–2960. https://doi.org/10.1172/JCI119848

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Sun Y, Ai X, Shen S, Lu S (2015) NF-κB-mediated miR-124 suppresses metastasis of non-small-cell lung cancer by targeting MYO10. Oncotarget 6(10):8244–8254. https://doi.org/10.18632/oncotarget.3135

    Article  PubMed  PubMed Central  Google Scholar 

  65. Singh S, Aggarwal BB (1995) Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J Biol Chem 270:24995–25000

    PubMed  CAS  Google Scholar 

  66. Lin YG, Kunnumakkara AB, Nair A, Merritt WM, Han LY, Armaiz-Pena GN (2007) Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway. Clin Cancer Res 13:3423–3430. https://doi.org/10.1158/1078-0432.CCR-06-3072

    Article  PubMed  CAS  Google Scholar 

  67. Nakamura K, Yasunaga Y, Segawa T, Ko D, Moul JW, Srivastava S (2002) Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. Int J Oncol 21:825–830. https://doi.org/10.3892/ijo.21.4.825

    Article  PubMed  CAS  Google Scholar 

  68. Zhang BY, Shi YQ, Chen X, Dai J, Jiang ZF, Li N et al (2013) Protective effect of curcumin against formaldehyde-induced genotoxicity in A549 Cell Lines. J Appl Toxicol 33:1468–1473. https://doi.org/10.1002/jat.2814

    Article  PubMed  CAS  Google Scholar 

  69. Kuo P, Chen MM, Decker RH, Yarbrough WG, Judson BL (2014) Hypopharyngeal cancer incidence, treatment, and survival: temporal trends in the United States. Laryngoscope 124(9):2064–2069. https://doi.org/10.1002/lary.24651

    Article  PubMed  Google Scholar 

  70. Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41(1):40–59. https://doi.org/10.1016/j.biocel.2008.06.010

    Article  CAS  Google Scholar 

  71. Vageli DP, Doukas SG, Spock T, Sasaki CT (2018) Curcumin prevents the bile reflux-induced NF-κB-related mRNA oncogenic phenotype, in human hypopharyngeal cells. J Cell Mol Med 22:4209–4220. https://doi.org/10.1111/jcmm.13701

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. LoTempio MM, Veena MS, Steele HL, Ramamurthy B, Ramalingam TS, Cohen AN, Wang MB (2005) Curcumin suppresses growth of head and neck squamous cell carcinoma. Clin Cancer Res 11(19):6994–7002. https://doi.org/10.1158/1078-0432.CCR-05-0301

    Article  PubMed  CAS  Google Scholar 

  73. Vander Broek R, Snow GE, Chen Z, Van Waes C (2014) Chemoprevention of head and neck squamous cell carcinoma through inhibition of NF-κB signaling. Oral Oncol 50(10):930–941. https://doi.org/10.1016/j.oraloncology.2013.10.005

    Article  PubMed  CAS  Google Scholar 

  74. Karin M (2006) Nuclear factor-κB in cancer development and progression. Nature 441(7092):431. https://doi.org/10.1038/nature04870

    Article  PubMed  CAS  Google Scholar 

  75. Xi Y, Gao H, Callaghan MU, Fribley AM, Garshott DM, Xu ZX (2015) Induction of BCL2-interacting killer, BIK, is mediated for anti-cancer activity of curcumin in human head and neck squamous cell carcinoma cells. J Cancer 6(4):327. https://doi.org/10.7150/jca.11185

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Calaf GM, Echiburú-Chau C, Roy D, Chai Y, Wen G, Balajee AS (2011) Protective role of curcumin in oxidative stress of breast cells. Oncol Rep 26(4):1029–1035. https://doi.org/10.3892/or.2011.1386

    Article  PubMed  CAS  Google Scholar 

  77. Liu Q, Loo WT, Sze SCW, Tong Y (2009) Curcumin inhibits cell proliferation of MDA-MB-231 and BT-483 breast cancer cells mediated by down-regulation of NFκB, cyclinD and MMP-1 transcription. Phytomedicine 16(10):916–922. https://doi.org/10.1016/j.phymed.2009.04.008

    Article  PubMed  CAS  Google Scholar 

  78. Bachmeier B, Nerlich A, Iancu C, Cilli M, Schleicher E, Vené R, Pfeffer U (2007) The chemopreventive polyphenol curcumin prevents hematogenous breast cancer metastases in immunodeficient mice. Cell Physiol Biochem 19(1-4):137–152. https://doi.org/10.1159/000099202

    Article  PubMed  CAS  Google Scholar 

  79. Kunnumakkara AB, Diagaradjane P, Anand P, Kuzhuvelil HB, Deorukhkar A, Gelovani J (2009) Curcumin sensitizes human colorectal cancer to capecitabine by modulation of cyclin D1, COX-2, MMP-9, VEGF and CXCR4 expression in an orthotopic mouse model. Int J Cancer 125(9):2187–2197. https://doi.org/10.1002/ijc.24593

    Article  PubMed  CAS  Google Scholar 

  80. Yodkeeree S, Ampasavate C, Sung B, Aggarwal BB, Limtrakul P (2010) Demethoxycurcumin suppresses migration and invasion of MDA-MB-231 human breast cancer cell line. Eur J Pharmacol 627(1-3):8–15. https://doi.org/10.1016/j.ejphar.2009.09.052

    Article  PubMed  CAS  Google Scholar 

  81. Xia Y, Jin L, Zhang B, Xue H, Li Q, Xu Y (2007) The potentiation of curcumin on insulin-like growth factor-1 action in MCF-7 human breast carcinoma cells. Life Sci 80(23):2161–2169. https://doi.org/10.1016/j.lfs.2007.04.008

    Article  PubMed  CAS  Google Scholar 

  82. Sahebkar A (2016) Curcumin: a natural multitarget treatment for pancreatic cancer. Integr Cancer Ther 15(3):333–334

    PubMed  PubMed Central  CAS  Google Scholar 

  83. Li L, Aggarwal BB, Shishodia S, Abbruzzese J, Kurzrock R (2004) Nuclear factor-kappaB and ikappaB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis. Cancer 101:2351–2362

    PubMed  CAS  Google Scholar 

  84. Bimonte S, Barbieri A, Palma G, Luciano A, Rea D, Arra C (2013). Curcumin inhibits tumor growth and angiogenesis in an orthotopic mouse model of human pancreatic cancer. Biomed Res. https://doi.org/10.1155/2013/810423

  85. Zhao Z, Li C, Xi H, Gao Y, Xu D (2015) Curcumin induces apoptosis in pancreatic cancer cells through the induction of forkhead box O1 and inhibition of the PI3K/Akt pathway. Mol Med Rep 12:5415–5422. https://doi.org/10.3892/mmr.2015.4060

    Article  PubMed  CAS  Google Scholar 

  86. Hosseini M, Hassanian SM, Mohammadzadeh E, ShahidSalesm S, Maftouh M, Fayazbakhsh H, Avan A (2017) Therapeutic potential of curcumin in treatment of pancreatic cancer: current status and future perspectives. J Cell Biochem 118(7):1634–1638. https://doi.org/10.1002/jcb.25897

    Article  PubMed  CAS  Google Scholar 

  87. Darvesh SA, Aggarwal BB, Bishayee A (2012) Curcumin and liver cancer: a review. Curr Pharm Biotechnol 13(1):218–228. https://doi.org/10.2174/138920112798868791

    Article  PubMed  CAS  Google Scholar 

  88. Jutooru I, Chadalapaka G, Lei P, Safe S (2010) Inhibition of NfkappaB and pancreatic cancer cell and tumor growth by curcumin is dependent on specificity protein down-regulation. J Biol Chem 285:25332–25344. https://doi.org/10.1074/jbc.M109.095240

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Basha R, Connelly SF, Sankpal UT, Nagaraju GP, Patel H, Vishwanatha JK, Shelake S, Tabor-Simecka L, Shoji M, Simecka JW, El-Rayes B (2016) Small molecule tolfenamic acid and dietary spice curcumin treatment enhances antiproliferative effect in pancreatic cancer cells via suppressing Sp1, disrupting NF-kB translocation to nucleus and cell cycle phase distribution. J Nutr Biochem 31:77–87. https://doi.org/10.1016/j.jnutbio.2016.01.003

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Marquardt JU, Gomez-Quiroz L, Camacho LOA, Pinna F, Lee YH, Kitade M (2015) Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer. J Hepatol 63(3):661–669. https://doi.org/10.1016/j.jhep.2015.04.018

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Zeng Y, Shen Z, Gu W, Mianhua W (2018) Inhibition of hepatocellular carcinoma tumorigenesis by curcumin may be associated with CDKN1A and CTGF. Gene 651:183–193. https://doi.org/10.1016/j.gene.2018.01.083

    Article  PubMed  CAS  Google Scholar 

  92. Pan Z, Zhuang J, Ji C, Cai Z, Liao W, Huang Z (2018) Curcumin inhibits hepatocellular carcinoma growth by targeting VEGF expression. Oncol Lett 15:4821–4826. https://doi.org/10.3892/ol.2018.7988

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Shukla S, Bhaskaran N, Babcook MA, Fu P, MacLennan GT, Gupta S (2013) Apigenin inhibits prostate cancer progression in TRAMP mice via targeting PI3K/Akt/FoxO pathway. Carcinogenesis 35(2):452–460

    PubMed  PubMed Central  Google Scholar 

  94. Shukla S, Kanwal R, Shankar E, Datt M, Chance MR, Fu P, Gupta S (2015) Apigenin blocks IKKα activation and suppresses prostate cancer progression. Oncotarget 6(31):31216

    PubMed  PubMed Central  Google Scholar 

  95. Chen M, Wang X, Zha D, Cai F, Zhang W, He Y, Huang Q, Zhuang H, Hua ZC (2016) Apigenin potentiates TRAIL therapy of non-small cell lung cancer via upregulating DR4/DR5 expression in a p53-dependent manner. Sci Rep 6(35468):1–17

    Google Scholar 

  96. Choi M (2017) Galangin suppresses pro-inflammatory gene expression in polyinosinic-polycytidylic acid-stimulated microglial cells. Biomol Ther 25(6):641–647. https://doi.org/10.4062/biomolther.2017.173

    Article  CAS  Google Scholar 

  97. Luo H, Rankin GO, Li Z, DePriest L, Chen YC (2011) Kaempferol induces apoptosis in ovarian cancer cells through activating p53 in the intrinsic pathway. Food Chem 128(2):513–519

    PubMed  PubMed Central  CAS  Google Scholar 

  98. Yang S, Si L, Jia Y, Jian W, Yu Q, Wang M, Lin R (2019) Kaempferol exerts anti-proliferative effects on human ovarian cancer cells by inducing apoptosis, G0/G1 cell cycle arrest and modulation of MEK/ERK and STAT3 pathways. J BUON 24:975–981

    PubMed  Google Scholar 

  99. Oyagbemi AA, Saba AB, Azeez OI (2010) Molecular targets of [6]-gingerol: Its potential roles in cancer chemoprevention. Biofactors 36(3):169–178

    PubMed  CAS  Google Scholar 

  100. Weng CJ, Chou CP, Ho CT, Yen GC (2012) Molecular mechanism inhibiting human hepatocarcinoma cell invasion by 6-shogaol and 6-gingerol. Mol Nutr Food Res 56(8):1304–1314. https://doi.org/10.1002/mnfr.201200173

    Article  PubMed  CAS  Google Scholar 

  101. Chakraborty D, Bishayee K, Ghosh S, Biswas R, Mandal SK, Khuda-Bukhsh AR (2012) [6]-Gingerol induces caspase 3 dependent apoptosis and autophagy in cancer cells Drug–DNA interaction and expression of certain signal genes in HeLa cells. Eur J Pharmacol 694(1-3):20–29

    PubMed  CAS  Google Scholar 

  102. Kim SO, Chun KS, Kundu JK, Surh YJ (2004) Inhibitory effects of [6]-gingerol on PMA-induced COX-2 expression and activation of NF-κB and p38 MAPK in mouse skin. Biofactors 21(1-4):27–31

    PubMed  Google Scholar 

  103. Park KK, Chun KS, Lee JM, Lee SS, Surh YJ (1998) Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice. Cancer Lett 129(2):139–144. https://doi.org/10.1016/S0304-3835(98)00081-0

    Article  PubMed  CAS  Google Scholar 

  104. Zhang F, Thakur K, Hu F, Zhang JG, Wei ZJ (2017) 10-Gingerol, a phytochemical derivative from “tongling white ginger”, inhibits cervical cancer: insights into the molecular mechanism and inhibitory targets. J Agric Food Chem 65(10):2089–2099. https://doi.org/10.1021/acs.jafc.7b00095

    Article  PubMed  CAS  Google Scholar 

  105. He W, Jiang Y, Zhang X, Zhang Y, Ji H, Zhang N (2014) Anticancer cardamonin analogs suppress the activation of NF-kappaB pathway in lung cancer cells. Mol Cell Biochem 389(1-2):25–33. https://doi.org/10.1007/s11010-013-1923-0

    Article  PubMed  CAS  Google Scholar 

  106. Pan MH, Hsieh MC, Kuo JM, Lai CS, Wu H, Sang S, Ho CT (2008) 6-Shogaol induces apoptosis in human colorectal carcinoma cells via ROS production, caspase activation, and GADD 153 expression. Mol Nutr Food Res 52(5):527–537. https://doi.org/10.1002/mnfr.200700157

    Article  PubMed  CAS  Google Scholar 

  107. Aggarwal BB, Sethi G, Ahn KS, Sandur SK, Pandey MK, Kunnumakkara AB (2006) Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann N Y Acad Sci 1091:151–169. https://doi.org/10.1196/annals.1378.063

    Article  PubMed  CAS  Google Scholar 

  108. Gupta SC, Kannappan R, Reuter S, Kim JH, Aggarwal BB (2011) Chemosensitization of tumors by resveratrol. Ann N Y Acad Sci 1215:150–160. https://doi.org/10.1111/j.1749-6632.2010.05852.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Bharti AC, Donato N, Aggarwal BB (2003) Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation inhuman multiple myeloma cells. J Immunol 171:3863–3871. https://doi.org/10.4049/jimmunol.171.7.3863

    Article  PubMed  CAS  Google Scholar 

  110. Pandey A, Vishnoi K, Mahata S, Tripathi SC, Misra SP, Misra V (2015) Berberine and curcumin target survivin and STAT3 in gastric cancer cells and synergize actions of standard chemotherapeutic 5-Fluorouracil. Nutr Cancer 67:1293–1304. https://doi.org/10.1080/01635581.2015.1085581

    Article  PubMed  CAS  Google Scholar 

  111. Fetoni AR, Paciello F, Mezzogori D, Rolesi R, Eramo SL, Paludetti G (2015) Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling. Br J Cancer 113:1434–1444. https://doi.org/10.1038/bjc.2015.359

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Wu SH, Hang LW, Yang JS, Chen HY, Lin HY, Chiang JH, Chung JG (2010) Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade-and mitochondria-dependent pathways. Anticancer Res 30(6):2125–2133

    PubMed  CAS  Google Scholar 

  113. Alexandrow MG, Song LJ, Altiok S, Gray J, Haura EB, Kumar NB (2012) Curcumin: a novel Stat3 pathway inhibitor for chemoprevention of lung cancer. Eur J Cancer Prev 21:407–412. https://doi.org/10.1097/CEJ.0b013e32834ef194

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL et al (2008) Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 14:4491–4499. https://doi.org/10.1158/1078-0432.CCR-08-0024

    Article  PubMed  CAS  Google Scholar 

  115. Vadhan-Raj S, Weber DM, Wang M, Giralt SA, Thomas SK, Alexanian R (2007) Curcumin downregulates NF-kB and related genes in patients with multiple myeloma: results of a phase I/II study. Blood 11:1177

    Google Scholar 

  116. Yang JY, Zhong X, Yum HW, Lee HJ, Kundu JK, Na HK (2013) Curcumin inhibits STAT3 signaling in the colon of dextran sulphate sodium-treated mice. J Cancer Prev 18:186–191. https://doi.org/10.15430/jcp.2013.18.2.18

    Article  PubMed  PubMed Central  Google Scholar 

  117. Kelkel M, Jacob C, Dicato M, Diederich M (2010) Potential of the dietary antioxidants resveratrol and curcumin in prevention and treatment of hematologic malignancies. Molecules 15(10):7035–7074. https://doi.org/10.3390/molecules15107035

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Kim SM, Kim C, Bae H, Lee JH, Baek SH, Nam D, Sethi G (2015) 6-Shogaol exerts anti-proliferative and pro-apoptotic effects through the modulation of STAT3 and MAPKs signaling pathways. Mol Carcinog 54(10):1132–1146

    PubMed  CAS  Google Scholar 

  119. Seo HS, Ku JM, Choi HS, Woo JK, Jang BH, Shin YC, Ko SG (2014) Induction of caspase-dependent apoptosis by apigenin by inhibiting STAT3 signaling in HER2-overexpressing MDA-MB-453 breast cancer cells. Anticancer Res 34:2869–2882

    PubMed  CAS  Google Scholar 

  120. Zhao X, Guo X, Shen J, Hua D (2018) Alpinetin inhibits proliferation and migration of ovarian cancer cells via suppression of STAT3 signaling. Mol Med Rep 18:4030–4036

    PubMed  CAS  Google Scholar 

  121. Zhang J, Sikka S, Siveen KS, Lee JH, Um JY, Kumar AP, Ahn KS (2017) Cardamonin represses proliferation, invasion, and causes apoptosis through the modulation of signal transducer and activator of transcription 3 pathway in prostate cancer. Apoptosis 22(1):158–168. https://doi.org/10.1007/s10495-016-1313-7

    Article  PubMed  CAS  Google Scholar 

  122. Wang Z, Tang X, Wu X, Yang M, Wang W, Wang L, Wang D (2019) Cardamonin exerts anti-gastric cancer activity via inhibiting LncRNA-PVT1-STAT3 axis. Biosci Rep 39(5):1–9. https://doi.org/10.1042/BSR20190357

    Article  Google Scholar 

  123. Jorvig JE, Chakraborty A (2015) Zerumbone inhibits growth of hormone refractory prostate cancer cells by inhibiting JAK2/STAT3 pathway and increases paclitaxel sensitivity. Anti-Cancer Drugs 26(2):160–166. https://doi.org/10.1097/CAD.0000000000000171

    Article  PubMed  CAS  Google Scholar 

  124. Shanmugam MK, Rajendran P, Li F, Kim C, Sikka S, Siveen KS, Sethi G (2015) Abrogation of STAT3 signaling cascade by zerumbone inhibits proliferation and induces apoptosis in renal cell carcinoma xenograft mouse model. Mol Carcinog 54(10):971–985. https://doi.org/10.1002/mc.22166

    Article  PubMed  CAS  Google Scholar 

  125. Kizhakkayil J, Thayyullathil F, Chathoth S, Hago A, Patel M, Galadari S (2010) Modulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K inhibitor in MCF-7 cells. Biochem Biophys Res Commun 394:476–481. https://doi.org/10.1016/j.bbrc.2010.01.132

    Article  PubMed  CAS  Google Scholar 

  126. Jin H, Qiao F, Wang Y, Xu Y, Shang Y (2015) Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway. Oncol Rep 34:2782–2789. https://doi.org/10.3892/or.2015.4258

    Article  PubMed  CAS  Google Scholar 

  127. Guan F, Ding Y, Zhang Y, Zhou Y, Li M, Wang C (2016) Curcumin suppresses proliferation and migration of MDA-MB-231 breast cancer cells through autophagy-dependent Akt degradation. PLoS ONE 11:e0146553. https://doi.org/10.1371/journal.pone.0146553

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Akkoc Y, Berrak O, Arsan ED, Obakan P, Coker-Gurkan A, Palavan-Unsal N (2015) Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is hindered by Bcl2 through activation of autophagy in MCF-7 cells. Biomed Pharmacother 71:161–171. https://doi.org/10.1016/j.biopha.2015.02.029

    Article  PubMed  CAS  Google Scholar 

  129. Lai HW, Chien SY, Kuo SJ, Tseng LM, Lin HY, Chi CW (2012) The potential utility of curcumin in the treatment of HER-2-overexpressedbreast cancer: an in vitro and in vivo comparison study with herceptin. Evid Based Complement Alternat Med 2012:486568. https://doi.org/10.1155/2012/486568

    Article  PubMed  Google Scholar 

  130. Tan BL, Norhaizan ME (2019) Curcumin combination chemotherapy: the implication and efficacy in cancer. Molecules 24(14):2527. https://doi.org/10.3390/molecules24142527

    Article  PubMed Central  CAS  Google Scholar 

  131. Hao F, Kang J, Cao Y (2015) Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic β-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways. Apoptosis 20:1420–1432. https://doi.org/10.1007/s10495-015-1150-0

    Article  PubMed  CAS  Google Scholar 

  132. Li XJ, Li Y, Jin CT, Fan J, Li HJ (2015) Curcumin induces apoptosis by PTEN/PI3K/AKT pathway in EC109 cells. Chin J Appl Physiol 31(2):174–177

    Google Scholar 

  133. Xu X, Qin J, Liu W (2014) Curcumin inhibits the invasion of thyroid cancer cells via down-regulation of PI3K/Akt signaling pathway. Gene 546:226–232. https://doi.org/10.1016/j.gene.2014.06.006

    Article  PubMed  CAS  Google Scholar 

  134. Jiang QG, Li TY, Liu DN, Zhang HT (2014) PI3K/Akt pathway involving into apoptosis and invasion in human colon cancer cells LoVo. Mol Biol Rep 41:3359–3367

    PubMed  CAS  Google Scholar 

  135. Qiao Q, Jiang Y, Li G (2013) Inhibition of the PI3K/AKT-NF-κB pathway with curcumin enhanced radiation-induced apoptosis in human Burkitt’s lymphoma. J Pharmacol Sci 121:247–256. https://doi.org/10.1254/jphs.12149FP

    Article  PubMed  CAS  Google Scholar 

  136. Zhao G, Han X, Zheng S, Li Z, Sha Y, Ni J (2016) Curcumin induces autophagy, inhibits proliferation and invasion by downregulating AKT/mTOR signaling pathway in human melanoma cells. Oncol Rep 35:1065–1074. https://doi.org/10.3892/or.2015.4413

    Article  PubMed  CAS  Google Scholar 

  137. Li B, Takeda T, Tsuiji K, Wong TF, Tadakawa M, Kondo A (2013) Curcumin induces cross-regulation between autophagy and apoptosis in uterine leiomyosarcoma cells. Int J Gynecol Cancer 23:803–808. https://doi.org/10.1097/IGC.0b013e31828c9581

    Article  PubMed  Google Scholar 

  138. Clark CA, McEachern MD, Shah SH, Rong Y, Rong X, Smelley CL (2010) Curcumin inhibits carcinogen and nicotine-induced mammalian target of rapamycin pathway activation in head and neck squamous cell carcinoma. Cancer Prev Res 3:1586–1595. https://doi.org/10.1158/1940-6207.CAPR-09-0244

    Article  CAS  Google Scholar 

  139. Kondo A, Takeda T, Li B, Tsuiji K, Kitamura M, Wong TF et al (2012) Epigallocatechin-3-gallate potentiates curcumin’s ability to suppress uterine leiomyosarcoma cell growth and induce apoptosis. Int J Clin Oncol 18:380–388. https://doi.org/10.1007/s10147-012-0387-7

    Article  PubMed  CAS  Google Scholar 

  140. Guo Y, Li Y, Shan Q, He G, Lin J, Gong Y (2015) Curcumin potentiates the anti-leukemia effects of imatinib by downregulation of the AKT/mTOR pathway and BCR/ABL gene expression in Ph+ acute lymphoblastic leukemia. Int J Biochem Cell Biol 65:1–11. https://doi.org/10.1016/j.biocel.2015.05.00

    Article  PubMed  CAS  Google Scholar 

  141. Lin CH, Chang CY, Lee KR, Lin HJ, Chen TH, Wan L (2015) Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway. BMC Cancer 15:958

    PubMed  PubMed Central  Google Scholar 

  142. Tong X, Pelling JC (2013) Targeting the PI3K/Akt/mTOR axis by apigenin for cancer prevention. Anti Cancer Agents Med Chem 13:971–978

    CAS  Google Scholar 

  143. Tong J, Shen Y, Zhang Z, Hu Y, Zhang X, Han L (2019) Apigenin inhibits epithelial-mesenchymal transition of human colon cancer cells through NF-κB/Snail signaling pathway. Biosci Rep 39(5). https://doi.org/10.1042/BSR20190452

  144. Yang J, Pi C, Wang G (2018) Inhibition of PI3K/Akt/mTOR pathway by apigenin induces apoptosis and autophagy in hepatocellular carcinoma cells. Biomed Pharmacother 103:699–707

    PubMed  CAS  Google Scholar 

  145. Chen X, Xu H, Yu X, Wang X, Zhu X, Xu X (2019) Apigenin inhibits in vitro and in vivo tumorigenesis in cisplatin-resistant colon cancer cells by inducing autophagy, programmed cell death and targeting mTOR/PI3K/Akt signalling pathway. J BUON 24:488–493

    PubMed  Google Scholar 

  146. Wu L, Yang W, Zhang SN, Lu JB (2015) Alpinetin inhibits lung cancer progression and elevates sensitization drug-resistant lung cancer cells to cis-diammined dichloridoplatium. Drug Des Devel Ther 9:6119–6127. https://doi.org/10.2147/DDDT.S92702

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  147. Wen M, Wu J, Luo H, Zhang H (2012) Galangin induces autophagy through upregulation of p53 in HepG2 cells. Pharmacology 89:247–255

    PubMed  CAS  Google Scholar 

  148. Lee CC, Lin ML, Meng M, Chen SS (2018) Galangin induces p53-independent S-phase arrest and apoptosis in human nasopharyngeal carcinoma cells through inhibiting PI3K–AKT signaling pathway. Anticancer Res 38(3):1377–1389

    PubMed  CAS  Google Scholar 

  149. Wang HX, Tang C (2017) Galangin suppresses human laryngeal carcinoma via modulation of caspase-3 and AKT signaling pathways. Oncol Rep 38(2):703–714

    PubMed  PubMed Central  CAS  Google Scholar 

  150. Meng B, Ii H, Qu W, Yuan H (2018) Anticancer effects of 6-gingerol in retinoblastoma cancer cells (RB355 Cell Line) are mediated via apoptosis induction, cell cycle arrest and upregulation of PI3K/Akt signaling pathway. Med Sci Monit 24:1980. https://doi.org/10.12659/msm.905450

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  151. Kapoor V, Aggarwal S, Das SN (2016) 6-Gingerol mediates its anti tumor activities in human oral and cervical cancer cell lines through apoptosis and cell cycle arrest. Phytother Res 30(4):588–595. https://doi.org/10.1002/ptr.5561

    Article  PubMed  CAS  Google Scholar 

  152. Joo JH, Hong SS, Cho YR, Seo DW (2016) 10-Gingerol inhibits proliferation and invasion of MDA-MB-231 breast cancer cells through suppression of Akt and p38MAPK activity. Oncol Rep 35(2):779–784

    PubMed  CAS  Google Scholar 

  153. Loung CY, Rasmussen AN, Hoskin DW (2019) The phenolic gingerols and gingerol-derived shogaols: features and properties related to the prevention and treatment of cancer and chronic inflammation. In: Polyphenols in plant. Academic, New York, pp 395–405. https://doi.org/10.1016/B978-0-12-813768-0.00024

    Chapter  Google Scholar 

  154. Hung JY, Hsu YL, Li CT, Ko YC, Ni WC, Huang MS, Kuo PL (2009) 6-Shogaol, an active constituent of dietary ginger, induces autophagy by inhibiting the AKT/mTOR pathway in human non-small cell lung cancer A549 cells. J Agric Food Chem 57(20):9809–9816. https://doi.org/10.1021/jf902315e

    Article  PubMed  CAS  Google Scholar 

  155. Zainal NS, Gan CP, Lau BF, San Yee P, Tiong KH, Rahman ZAA, Cheong SC (2018) Zerumbone targets the CXCR4-RhoA and PI3K-mTOR signaling axis to reduce motility and proliferation of oral cancer cells. Phytomedicine 39:33–41

    PubMed  CAS  Google Scholar 

  156. Kang CG, Lee HJ, Kim SH, Lee EO (2015) Zerumbone suppresses osteopontin-induced cell invasion through inhibiting the FAK/AKT/ROCK pathway in human non-small cell lung cancer A549 cells. J Nat Prod 79(1):156–160

    PubMed  Google Scholar 

  157. Kashafi E, Moradzadeh M, Mohamadkhani A, Erfanian S (2017) Kaempferol increases apoptosis in human cervical cancer HeLa cells via PI3K/AKT and telomerase pathways. Biomed Pharmacother 89:573–577

    PubMed  CAS  Google Scholar 

  158. Yang J, Xiao P, Sun J, Guo L (2018) Anticancer effects of kaempferol in A375 human malignant melanoma cells are mediated via induction of apoptosis, cell cycle arrest, inhibition of cell migration and downregulation of m-TOR/PI3K/AKT pathway. J BUON 23:218–223

    PubMed  Google Scholar 

  159. Break MKB, Hossan MS, Khoo Y, Qazzaz ME, Al-Hayali MZ, Chow SC, Khoo TJ (2018) Discovery of a highly active anticancer analogue of cardamonin that acts as an inducer of caspase-dependent apoptosis and modulator of the mTOR pathway. Fitoterapia 125:161–173. https://doi.org/10.1016/j.fitote.2018.01.006

    Article  PubMed  CAS  Google Scholar 

  160. Chen H, Tang X, Liu T, Jing L, Wu J (2019) Zingiberene inhibits in vitro and in vivo human colon cancer cell growth via autophagy induction, suppression of PI3K/AKT/mTOR pathway and caspase 2 deactivation. J BUON 24(4):1470–1475

    PubMed  Google Scholar 

  161. Nagy LI, Fehér LZ, Szebeni GJ, Gyuris M, Sipos P, Alföldi R (2015) Curcumin and its analogue induce apoptosis in leukemia cells and have additive effects with bortezomib in cellular and xenograft models. BioMed Res. https://doi.org/10.1155/2015/968981

  162. Jagetia GC, Aggarwal BB (2007) “Spicing up” of the immune system by curcumin. Clin Immunol 27(1):19–35. https://doi.org/10.1007/s10875-006-9066-7

    Article  CAS  Google Scholar 

  163. Shanbhag VKL (2017) Curcumin in chronic lymphocytic leukemia–A review. Asian Pac J Trop Biomed 7(6):505–512. https://doi.org/10.1016/j.apjtb.2017.05.003

    Article  Google Scholar 

  164. Park S, Cho DH, Andera L, Suh N, Kim I (2013) Curcumin enhances TRAIL-induced apoptosis of breast cancer cells by regulating apoptosis-related proteins. Mol Cell Biochem 383(1-2):39–48. https://doi.org/10.1007/s11010-013-1752-1

    Article  PubMed  CAS  Google Scholar 

  165. Díaz Osterman CJ, Gonda A, Stiff T, Sigaran U, Valenzuela MM, Ferguson Bennit HR et al (2016) Curcumin induces pancreatic adenocarcinoma cell death via reduction of the inhibitors of apoptosis. Pancreas 45(1):101–109. https://doi.org/10.1097/MPA.0000000000000411

    Article  PubMed  CAS  Google Scholar 

  166. Sarkar S, Dubaybo H, Ali S, Goncalves P, Kollepara SL, Sethi S (2013) Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27kip1, p57kip2, and PUMA. Am J Cancer Res 3(5):465

    PubMed  PubMed Central  Google Scholar 

  167. Sun XD, Liu XE, Huang DS (2013) Curcumin reverses the epithelial-mesenchymal transition of pancreatic cancer cells by inhibiting the Hedgehog signaling pathway. Oncol Rep 29(6):2401–2407. https://doi.org/10.3892/or.2013.2385

    Article  PubMed  CAS  Google Scholar 

  168. Song W, Yan CY, Zhou QQ, Zhen LL (2017) Galangin potentiates human breast cancer to apoptosis induced by TRAIL through activating AMPK. Biomed Pharmacother 89:845–856

    PubMed  CAS  Google Scholar 

  169. Ozbey U, Attar R, Romero MA, Alhewairini SS, Afshar B, Sabitaliyevich UY, Farooqi AA (2019) Apigenin as an effective anticancer natural product: spotlight on TRAIL, WNT/β-catenin, JAK-STAT pathways, and microRNAs. J Cell Biochem 120(2):1060–1067

    CAS  Google Scholar 

  170. Yodkeeree S, Sung B, Limtrakul P, Aggarwal BB (2009) Zerumbone enhances TRAIL-induced apoptosis through the induction of death receptors in human colon cancer cells: Evidence for an essential role of reactive oxygen species. Cancer Res 69(16):6581–6589

    PubMed  PubMed Central  CAS  Google Scholar 

  171. Gao Y, Yin J, Rankin G, Chen Y (2018) Kaempferol induces G2/M cell cycle arrest via checkpoint kinase 2 and promotes apoptosis via death receptors in human ovarian carcinoma A2780/CP70 Cells. Molecules 23(5):1095. https://doi.org/10.3390/molecules23051095

    Article  PubMed Central  CAS  Google Scholar 

  172. Kashyap D, Sharma A, Tuli HS, Sak K, Punia S, Mukherjee TK (2017) Kaempferol–A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements. J Funct Foods 30:203–219

    PubMed  PubMed Central  CAS  Google Scholar 

  173. Imran M, Salehi B, Sharifi-Rad J, Aslam Gondal T, Saeed F, Imran A, Shahbaz M, Tsouh Fokou PV, Umair Arshad M, Khan H, Guerreiro SG, Martins N, Estevinho LM (2019) Kaempferol: a key emphasis to its anticancer potential. Molecules 24(12):2277. https://doi.org/10.3390/molecules24122277

    Article  PubMed Central  CAS  Google Scholar 

  174. Yarden Y (2001) The EGFR family and its ligands in human cancer: signalling mechanisms and therapeutic opportunities. Eur J Cancer 37:S3–S8. https://doi.org/10.1016/S0959-8049(01)00230-1

    Article  PubMed  CAS  Google Scholar 

  175. Starok M, Preira P, Vayssade M, Haupt K, Salome L, Rossi C (2015) EGFR inhibition by curcumin in cancer cells: a dual mode of action. Biomacromolecules 16:1634–1642. https://doi.org/10.1021/acs.biomac.5b00229

    Article  PubMed  CAS  Google Scholar 

  176. Bojko A, Cierniak A, Adamczyk A, Ligeza J (2015) Modulatory effects of curcumin and tyrphostins (AG494 and AG1478) on growth regulation and viability of LN229 human brain cancer cells. Nutr Cancer 67:1170–1182. https://doi.org/10.1080/01635581.2015.1073764

    Article  PubMed  CAS  Google Scholar 

  177. Li S, Liu Z, Zhu F, Fan X, Wu X, Zhao H (2013) Curcumin lowers erlotinib resistance in non-small cell lung carcinoma cells with mutated EGF receptor. Oncol Res 21:137–144. https://doi.org/10.3727/096504013X13832473330032

    Article  PubMed  CAS  Google Scholar 

  178. Lev-Ari S, Starr A, Vexler A, Karaush V, Loew V, Greif J (2006) Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity. Anticancer Res 26:4423–4430

    PubMed  CAS  Google Scholar 

  179. Chen JW, Tang YL, Liu H, Zhu ZY, Lü D, Geng N, Chen Y (2011) Anti-proliferative and anti-metastatic effects of curcumin on oral cancer cells. Hua xi kou qiang yi xue za zhi Huaxi kouqiang yixue zazhi. West Chin J Stomatol 29(1):83–86

    CAS  Google Scholar 

  180. Yoysungnoen-Chintana P, Bhattarakosol P, Patumraj S (2014) Antitumor and antiangiogenic activities of curcumin in cervical cancer xenografts in nude mice. Biomed Res Int 2014:817972. https://doi.org/10.1155/2014/817972

    Article  PubMed  PubMed Central  Google Scholar 

  181. Wang S, Yu S, Shi W, Ge L, Yu X, Fan J (2011) Curcumin inhibits the migration and invasion of mouse hepatoma Hca-F cells through down-regulating caveolin-1 expression and epidermal growth factor receptor signaling. IUBMB Life 63:775–782. https://doi.org/10.1002/iub.507

    Article  PubMed  CAS  Google Scholar 

  182. Sun XD, Liu XE, Huang DS (2012) Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EGFR expression. Mol Med Rep 6(6):1267–1270. https://doi.org/10.3892/mmr.2012.1103

    Article  PubMed  CAS  Google Scholar 

  183. Somers-Edgar TJ, Scandlyn MJ, Stuart EC, Le Nedelec MJ, Valentine SP, Rosengren RJ (2008) The combination of epigallocatechin gallate and curcumin suppresses ER alpha-breast cancer cell growth in vitro and in vivo. Int J Cancer 122:1966–1971. https://doi.org/10.1002/ijc.23328

    Article  PubMed  CAS  Google Scholar 

  184. Zhan Y, Chen Y, Liu R, Zhang H, Zhang Y (2014) Potentiation of paclitaxel activity by curcumin in human breast cancer cell by modulating apoptosis and inhibiting EGFR signaling. Arch Pharm Res 37:1086–1095. https://doi.org/10.1007/s12272-013-0311

    Article  PubMed  CAS  Google Scholar 

  185. Lee JY, Lee YM, Chang GC, Yu SL, Hsieh WY, Chen JJ (2011) Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: the versatile adjuvant for gefitinib therapy. PLoS ONE 6:e23756. https://doi.org/10.1371/journal.pone.0023756

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  186. Lv T, Zhang W, Han X (2018) Zerumbone suppresses the potential of growth and metastasis in hepatoma HepG2 cells via the MAPK signaling pathway. Oncol Lett 15(5):7603–7610

    PubMed  PubMed Central  Google Scholar 

  187. Pham H, Chen M, Takahashi H, King J, Reber HA, Hines OJ, Pandol S, Eibl G (2012) Apigenin inhibits NNK-induced focal adhesion kinase activation in pancreatic cancer cells. Pancreas 41:1306–1315

    PubMed  PubMed Central  CAS  Google Scholar 

  188. Kwak MK, Yang KM, Park J, Lee S, Park Y, Hong E, Lee J (2017) Galangin enhances TGF-β1-mediated growth inhibition by suppressing phosphorylation of threonine 179 residue in Smad3 linker region. Biochem Biophys Res 494(3-4):706–713

    CAS  Google Scholar 

  189. Lei D, Zhang F, Yao D, Xiong N, Jiang X, Zhao H (2018) Galangin increases ERK1/2 phosphorylation to decrease ADAM9 expression and prevents invasion in A172 glioma cells. Mol Med Rep 17:667–673. https://doi.org/10.3892/mmr.2017.7920

    Article  PubMed  CAS  Google Scholar 

  190. Dang Q, Song W, Xu D, Ma Y, Li F, Zeng J, Li L (2015) Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis. Mol Carcinog 54(9):831–840

    PubMed  CAS  Google Scholar 

  191. Hung TW, Chen PN, Wu HC, Wu SW, Tsai PY, Hsieh YS, Chang HR (2017) Kaempferol inhibits the invasion and migration of renal cancer cells through the downregulation of AKT and FAK pathways. Int J Res Med Sci 14(10):984. https://doi.org/10.7150/ijms.20336

    Article  CAS  Google Scholar 

  192. Mohamed HE, Badawy MM (2019) Modulatory effect of zingerone against cisplatin or γ-irradiation induced hepatotoxicity by molecular targeting regulation. Appl Radiat Isot 154:108891. https://doi.org/10.1016/j.apradiso.2019.10889

    Article  PubMed  CAS  Google Scholar 

  193. Kwak MK, Kensler TW (2010) Targeting NRF2 signaling for cancer chemoprevention. Toxicol Appl Pharmacol 244:66–76. https://doi.org/10.1016/j.taap.2009.08.028

    Article  PubMed  CAS  Google Scholar 

  194. Ashrafizadeh M, Ahmadi Z, Mohamamdinejad R, Farkhondeh T, Samarghandian S (2020) Curcumin activates the Nrf2 pathway and induces cellular protection against oxidative injury. Curr Mol Med 20(2):116–133. https://doi.org/10.2174/1566524019666191016150757

    Article  PubMed  CAS  Google Scholar 

  195. Boyanapalli SS, Paredes-Gonzalez X, Fuentes F, Zhang C, Guo Y, Pung D (2014) Nrf2 knockout attenuates the anti-inflammatory effects of phenethyl isothiocyanate and curcumin. Chem Res Toxicol 27:2036–2043. https://doi.org/10.1021/tx500234h

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  196. Khor TO, Huang Y, Wu TY, Shu L, Lee J, Kong AN (2011) Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation. Biochem Pharmacol 82:1073–1078. https://doi.org/10.1016/j.bcp.2011.07.065

    Article  PubMed  CAS  Google Scholar 

  197. Avtanski D, Poretsky L (2018) Phyto-polyphenols as potential inhibitors of breast cancer metastasis. Mol Med 24(1):29

    PubMed  PubMed Central  Google Scholar 

  198. Chen J, Wang FL, Chen WD (2014) Modulation of apoptosis-related cell signaling pathways by curcumin as a strategy to inhibit tumor progression. Mol Biol Rep 41:4583–4594. https://doi.org/10.1007/s11033-014-3329-

    Article  PubMed  CAS  Google Scholar 

  199. DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K (2011) Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 475(7354):106. https://doi.org/10.1038/nature10189

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  200. Zhang SN, Yong Q, Wu XL, Liu XP (2014) Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and its related mechanism. ZhongYaoCai 37:2043–2046

    PubMed  CAS  Google Scholar 

  201. Fang D, Xiong Z, Xu J, Yin J, Luo R (2019) Chemopreventive mechanisms of galangin against hepatocellular carcinoma: a review. Biomed Pharmacother 109:2054–2061

    PubMed  CAS  Google Scholar 

  202. Li Y, Guo M, Lin Z, Zhao M, Xia Y, Wang C, Zhu B (2018) Multifunctional selenium nanoparticles with Galangin-induced HepG2 cell apoptosis through p38 and AKT signalling pathway. R Soc Open Sci 5(11):180509. https://doi.org/10.1098/rsos.180509

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  203. Kumar R, Tiku AB (2018) Galangin induces cell death by modulating the expression of glyoxalase-1 and Nrf-2 in HeLa cells. Chem Biol Interact 279:1–9. https://doi.org/10.1016/j.cbi.2017.11.001

    Article  PubMed  CAS  Google Scholar 

  204. Zhang L, Cheng X, Gao Y, Zheng J, Xu Q, Sun Y, Sun Z (2015) Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells. Food Funct 6(11):3464–3472

    PubMed  CAS  Google Scholar 

  205. Impheng H, Richert L, Pekthong D, Scholfield CN, Pongcharoen S, Pungpetchara I, Srisawang P (2015) [6]-Gingerol inhibits de novo fatty acid synthesis and carnitine palmitoyltransferase-1 activity which triggers apoptosis in HepG2. Am J Cancer Res 5(4):1319

    PubMed  PubMed Central  CAS  Google Scholar 

  206. Yang G, Wang S, Zhong L, Dong X, Zhang W, Jiang L, Ma Y (2012) 6-Gingerol induces apoptosis through lysosomal-mitochondrial axis in human hepatoma G2 cells. Phytother Res 26(11):1667–1673

    PubMed  CAS  Google Scholar 

  207. Rastogi N, Duggal S, Singh SK, Porwal K, Srivastava VK, Maurya R, Mishra DP (2015) Proteasome inhibition mediates p53 reactivation and anti-cancer activity of 6-gingerol in cervical cancer cells. Oncotarget 6(41):43310. https://doi.org/10.18632/oncotarget.6383

    Article  PubMed  PubMed Central  Google Scholar 

  208. Liang T, He Y, Chang Y, Liu X (2019) 6-shogaol a active component from ginger inhibits cell proliferation and induces apoptosis through inhibition of STAT-3 translocation in ovarian cancer cell lines (A2780). Biotechnol Bioproc E 24(3):560–567

    CAS  Google Scholar 

  209. Ryu MJ, Chung HS (2015) [10]-Gingerol induces mitochondrial apoptosis through activation of MAPK pathway in HCT116 human colon cancer cells. In Vitro Cell Dev Biol Anim 51(1):92–101. https://doi.org/10.1007/s11626-014-9806-6

    Article  PubMed  CAS  Google Scholar 

  210. Sithara T, Dhanya BP, Arun KB, Sini S, Dan M, Kokkuvayil Vasu R, Nisha P (2018) Zerumbone, a cyclic sesquiterpene from Zingiber zerumbet induces apoptosis, cell cycle arrest, and antimigratory effects in SW480 colorectal cancer cells. J Agric Food Chem 66(3):602–612. https://doi.org/10.1021/acs.jafc.7b04472

    Article  PubMed  CAS  Google Scholar 

  211. Yan H, Ren MY, Wang ZX, Feng SJ, Li S, Cheng Y, Zhang GQ (2017) Zerumbone inhibits melanoma cell proliferation and migration by altering mitochondrial functions. Oncol Lett 13(4):2397–2402. https://doi.org/10.3892/ol.2017.5742

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  212. Girisa S, Shabnam B, Monisha J, Fan L, Halim CE, Arfuso F, Kunnumakkara AB (2019) Potential of zerumbone as an anti-cancer agent. Molecules 24(4):734. https://doi.org/10.3390/molecules24040734

    Article  PubMed Central  CAS  Google Scholar 

  213. Zhou YZ, Tu WW, Shu CZ, Gu XF, Huang Y, Shen XJ, Gu HF (2017) Zerumbone induces G1 cell cycle arrest and apoptosis in cervical carcinoma cells. Int J Clin Exp Med 10(4):6640–6647

    CAS  Google Scholar 

  214. Deorukhkar A, Ahuja N, Mercado AL, Diagaradjane P, Raju U (2015) Zerumbone increases oxidative stress in a thiol-dependent ROS-independent manner to increase DNA damage and sensitize colorectal cancer cells to radiation. Cancer Med 4(2):278–292

    PubMed  CAS  Google Scholar 

  215. Chiang PK, Tsai WK, Chen M, Lin WR, Chow YC, Lee CC, Chen YJ (2018) Zerumbone regulates DNA repair responding to ionizing radiation and enhances radiosensitivity of human prostatic cancer cells. Integr Cancer Ther 17(2):292–298

    PubMed  CAS  Google Scholar 

  216. Choi EM (2011) Kaempferol protects MC3T3-E1 cells through antioxidant effect and regulation of mitochondrial function. Food Chem Toxicol 49(8):1800–1805

    PubMed  CAS  Google Scholar 

  217. Kalyani C, Narasu ML, Devi YP (2017) Synergistic growth inhibitory effect of flavonol–kaempferol and conventional chemotherapeutic drugs on cancer cells. Int J Pharm Pharm Sci 9:123–127

    CAS  Google Scholar 

  218. Imran M, Rauf A, Shah ZA, Saeed F, Imran A, Arshad MU, Mubarak MS (2019) Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: a comprehensive review. Phytother Res 33(2):263–275

    PubMed  Google Scholar 

  219. Berning L, Scharf L, Aplak E, Stucki D, von Montfort C, Reichert AS, Brenneisen P (2019) In vitro selective cytotoxicity of the dietary chalcone cardamonin (CD) on melanoma compared to healthy cells is mediated by apoptosis. PLoS One 14(9). https://doi.org/10.1371/journal.pone.0222267

  220. Su P, Veeraraghavan VP, Mohan SK, Lu W (2019) A ginger derivative, zingerone—a phenolic compound—induces ROS-mediated apoptosis in colon cancer cells (HCT-116). J Biochem Mol Toxicol 2019:e22403. https://doi.org/10.1002/jbt.22403

    Article  CAS  Google Scholar 

  221. Vinothkumar R, Sudha M, Nalini N (2014) Chemopreventive effect of zingerone against colon carcinogenesis induced by 1,2-dimethylhydrazine in rats. Eur J Cancer Prev 23(5):361–371. https://doi.org/10.1097/CEJ.0b013e32836473ac

    Article  PubMed  CAS  Google Scholar 

  222. Ganaie MA, Al Saeedan A, Madhkali H, Jan BL, Khatlani T, Sheikh IA, Wani K (2019) Chemopreventive efficacy zingerone (4-[4-hydroxy-3-methylphenyl] butan-2-one) in experimental colon carcinogenesis in Wistar rats. Environ Toxicol 34(5):610–625. https://doi.org/10.1002/tox.22727

    Article  PubMed  CAS  Google Scholar 

  223. Shieh PC, Chen YO, Kuo DH, Chen FA, Tsai ML, Chang IS, Pan MH (2010) Induction of apoptosis by [8]-shogaol via reactive oxygen species generation, glutathione depletion, and caspase activation in human leukemia cells. J Agric Food Chem 58(6):3847–3854

    PubMed  PubMed Central  CAS  Google Scholar 

  224. Subramaniam D, Ramalingam S, Houchen CW, Anant S (2010) Cancer stem cells: a novel paradigm for cancer prevention and treatment. Mini Rev Med Chem 10:359–371. https://doi.org/10.2174/138955710791330954

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  225. Banik U, Parasuraman S, Adhikary AK, Othman NH (2017) Curcumin: the spicy modulator of breast carcinogenesis. J Exp Clin Cancer Res 36(1):98

    PubMed  PubMed Central  Google Scholar 

  226. Subramaniam D, Ponnurangam S, Ramamoorthy P, Standing D, Battafarano RJ, Anant S (2012) Curcumin induces cell death in esophageal cancer cells through modulating Notch signaling. PLoS One 7:e30590. https://doi.org/10.1371/journal.pone.0030590

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  227. Kunnumakkara AB, Anand P, Aggarwal BB (2008) Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett 269(2):199–225. https://doi.org/10.1016/j.canlet.2008.03.009

    Article  PubMed  CAS  Google Scholar 

  228. Ghosh AK, Kay NE, Secreto CR, Shanafelt TD (2009) Curcumin inhibits prosurvival pathways in chronic lymphocytic leukemia B cells and may overcome their stromal protection in combination with EGCG. Clin Cancer Res 15(4):1250–1258. https://doi.org/10.1158/1078-0432.CCR-08-1511

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  229. Bimonte S, Barbieri A, Leongito M, Piccirillo M, Giudice A, Pivonello C, Izzo F (2016) Curcumin anticancer studies in pancreatic cancer. Nutrients 8(7):433

    PubMed Central  Google Scholar 

  230. Ray A, Vasudevan S, Sengupta S (2015) 6-Shogaol inhibits breast cancer cells and stem cell-like spheroids by modulation of Notch signaling pathway and induction of autophagic cell death. PLoS One 10(9):e0137614

    PubMed  PubMed Central  Google Scholar 

  231. Guo Y, Chen Y, Liu H, Yan W (2019) Alpinetin inhibits oral squamous cell carcinoma proliferation via miR-211-5p upregulation and notch pathway deactivation. Nutr Cancer 72(5):757–767

    PubMed  Google Scholar 

  232. Wang J, Yan Z, Liu X, Che S, Wang C (2016) Alpinetin targets glioma stem cells by suppressing notch pathway. Tumor Biol 37:9243–9248. https://doi.org/10.1007/s13277-016-4827-2

    Article  CAS  Google Scholar 

  233. Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. Nat Cell Biol 4(5):E131. https://doi.org/10.1038/ncb0502-e131

    Article  PubMed  CAS  Google Scholar 

  234. Liu S, Wang Z, Hu Z, Zeng X, Li Y, Su Y (2011) Anti-tumor activity of curcumin against androgen-independent prostate cancer cells via inhibition of NF-κB and AP-1 pathway in vitro. J Huazhong Univ Sci Technolog Med Sci 31:530–534. https://doi.org/10.1007/s11596-011-0485-1

    Article  PubMed  CAS  Google Scholar 

  235. Das L, Vinayak M (2014) Curcumin attenuates carcinogenesis by down regulating proinflammatory cytokine interleukin-1 (IL-1α and IL-1β) via modulation of AP-1 and NF-IL6 in lymphoma bearing mice. Int Immunopharmacol 20:141–147. https://doi.org/10.1016/j.intimp.2014.02.024

    Article  PubMed  CAS  Google Scholar 

  236. Yang CW, Chang CL, Lee HC, Chi CW, Pan JP, Yang WC (2012) Curcumin induces the apoptosis of human monocytic leukemia THP-1cells via the activation of JNK/ERK pathways. BMC Complement Altern Med 12:22. https://doi.org/10.1186/1472-6882-12-22

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  237. Chien ST, Shi MD, Lee YC, Te CC, Shih YW (2015) Galangin, a novel dietary flavonoid, attenuates metastatic feature via PKC/ERK signaling pathway in TPA-treated liver cancer HepG2 cells. Cancer Cell Int 15(1):15

    PubMed  PubMed Central  Google Scholar 

  238. Bertl E, Bartsch H, Gerhäuser C (2006) Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention. Mol Cancer Ther 5:575–585

    PubMed  CAS  Google Scholar 

  239. Bae MK, Kim SH, Jeong JW, Lee YM, Kim HS, Kim SR (2006) Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1. Oncol Rep 15:1557–1562. https://doi.org/10.3892/or.15.6.1557

    Article  PubMed  CAS  Google Scholar 

  240. Upadhyay J, Kesharwani RK, Misra K (2009) Comparative study of antioxidants as cancer preventives through inhibition of HIF-1 alpha activity. Bioinformation 4(6):233–236. https://doi.org/10.6026/97320630004233

    Article  PubMed  PubMed Central  Google Scholar 

  241. Shan B, Schaaf C, Schmidt A, Lucia K, Buchfelder M, Losa M (2012) Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas. J Endocrinol 214:389–398

    PubMed  CAS  Google Scholar 

  242. Lee SS, Tsai CH, Yang SF, Ho YC, Chang YC (2010) Hypoxia inducible factor-1α expression in areca quid chewing-associated oral squamous cell carcinomas. Oral Dis 16:696–701. https://doi.org/10.1111/j.1601-0825.2010.01680.x

    Article  PubMed  Google Scholar 

  243. Ye MX, Zhao YL, Li Y, Miao Q, Li ZK, Ren XL (2012) Curcumin reverses cisplatin resistance and promotes human lung adenocarcinoma A549/DDP cell apoptosis through HIF-1α and caspase-3 mechanisms. Phytomedicine 19:779–787. https://doi.org/10.1016/j.phymed.2012.03.005

    Article  PubMed  CAS  Google Scholar 

  244. Lee C, Yang J, Tsai F, Chiang N, Lu C, Huang Y, Chen F (2016) Kaempferol induces ATM/p53-mediated death receptor and mitochondrial apoptosis in human umbilical vein endothelial cells. Int J Oncol 48:2007–2014. https://doi.org/10.3892/ijo.2016.3420

    Article  PubMed  CAS  Google Scholar 

  245. Chin HK, Horng CT, Liu YS, Lu CC, Su CY, Chen PS, Yang JS (2018) Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells. Oncol Rep 39(5):2351–2357. https://doi.org/10.3892/or.2018.6312

    Article  PubMed  CAS  Google Scholar 

  246. Luo H, Rankin GO, Liu L, Daddysman MK, Jiang B-H, Chen YC (2009) Kaempferol inhibits angiogenesis and VEGF expression through both HIF dependent and independent pathways in human ovarian cancer cells. Nutr Cancer 61(4):554–563. https://doi.org/10.1080/01635580802666281

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  247. Park JH, Park GM, Kim JK (2015) Zerumbone, sesquiterpene photochemical from ginger, inhibits angiogenesis. Korean J Physiol Pharm 19(4):335–340

    CAS  Google Scholar 

  248. Samad NA, Abdul AB, Rahman HS, Rasedee A, Ibrahim TAT, Keon YS (2017) Zerumbone suppresses angiogenesis in HepG2 cells through inhibition of matrix Metalloproteinase-9, vascular endothelial growth factor, and vascular endothelial growth factor receptor expressions. Pharmacogn Mag 13(Suppl 4):S731

    Google Scholar 

  249. Samad NA, Abdul AB, Rahman HS, Abdullah R, Ibrahim TAT, Othman HH (2019) Antiproliferative and antiangiogenic effects of zerumbone from Zingiber zerumbet L. Smith in sprague dawley rat model of hepatocellular carcinoma. Pharmacogn Mag 15(61):277. https://doi.org/10.4103/pm.pm_118_18

    Article  CAS  Google Scholar 

  250. Huang H, Chen AY, Rojanasakul Y, Ye X, Rankin GO, Chen YC (2015) Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis. J Funct Foods 15:464–475. https://doi.org/10.1016/j.jff.2015.03.051

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  251. Chen D, Li D, Xu XB, Qiu S, Luo S, Qiu E, Zheng D (2019) Galangin inhibits epithelial-mesenchymal transition and angiogenesis by downregulating CD44 in glioma. J Cancer 10(19):4499–4508. https://doi.org/10.7150/jca.31487

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  252. Bae WY, Choi JS, Kim JE, Park C, Jeong JW (2016) Zingerone suppresses angiogenesis via inhibition of matrix metalloproteinases during tumor development. Oncotarget 7(30):47232. https://doi.org/10.18632/oncotarget.10030

    Article  PubMed  PubMed Central  Google Scholar 

  253. He J, Xu Q, Wang M, Qian X, Shi Z, Jiang BH (2012) Oral administration of apigenin inhibits metastasis through AKT/P70S6K1/MMP-9 pathway in orthotopic ovarian tumor model. Int J Mol 13(6):7271–7282. https://doi.org/10.3390/ijms13067271

    Article  CAS  Google Scholar 

  254. Pai SG, Carneiro BA, Mota JM, Costa R, Leite CA, Barroso-Sousa R, Giles FJ (2017) Wnt/beta-catenin pathway: modulating anticancer immune response. J Hematol Oncol 10:101. https://doi.org/10.1186/s13045-017-0471-6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  255. Mukherjee S, Mazumdar M, Chakraborty S, Manna A, Saha S, Khan P (2014) Curcumin inhibits breast cancer stem cell migration by amplifying the E-cadherin/β-catenin negative feedback loop. Stem Cell Res Ther 5:116. https://doi.org/10.1186/scrt506

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  256. Sundram V, Chauhan SC, Ebeling M, Jaggi M (2012) Curcumin attenuates β-catenin signaling in prostate cancer cells through activation of protein kinase D1. PLoS ONE 7:e35368. https://doi.org/10.1371/journal.pone.0035368

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  257. Choi HY, Lim JE, Hong JH (2010) Curcumin interrupts the interaction between the androgen receptor and Wnt/β-catenin signaling pathway in LNCaP prostate cancer cells. Prostate Cancer Prostatic Dis 13:343–349. https://doi.org/10.1038/pcan.2010.26

    Article  PubMed  CAS  Google Scholar 

  258. Yallapu MM, Khan S, Maher DM, Ebeling MC, Sundram V, Chauhan N (2014) Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer. Biomaterials 35:8635–8648. https://doi.org/10.1016/j.biomaterials.2014.06.04

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  259. Lu Y, Wei C, Xi Z (2014) Curcumin suppresses proliferation and invasion in non-small cell lung cancer by modulation of MTA1-mediated Wnt/β-catenin pathway. In Vitro Cell Dev Biol Anim 50:840–850. https://doi.org/10.1007/s11626-014-9779-5

    Article  PubMed  CAS  Google Scholar 

  260. Dermani FK, Amini R, Saidijam M, Pourjafar M, Saki S, Najafi R (2018) Zerumbone inhibits epithelial-mesenchymal transition and cancer stem cells properties by inhibiting the β-catenin pathway through miR-200c. J Cell Physiol 233(12):9538–9547. https://doi.org/10.1002/jcp.26874

    Article  PubMed  CAS  Google Scholar 

  261. Fatima A, Abdul ABH, Abdullah R, Karjiban RA, Lee VS (2018) Docking studies reveal zerumbone targets β-catenin of the Wnt–β-catenin pathway in breast cancer. J Serb Chem Soc 83(5):575–591. https://doi.org/10.2298/JSC170313108F

    Article  CAS  Google Scholar 

  262. Liu X, Li L, Lv L, Chen D, Shen L, Xie Z (2015) Apigenin inhibits the proliferation and invasion of osteosarcoma cells by suppressing the Wnt/beta-catenin signaling pathway. Oncol Rep 34:1035–1041. https://doi.org/10.3892/or.2015.4022

    Article  PubMed  CAS  Google Scholar 

  263. Xu M, Wang S, Song YU, Yao J, Huang K, Zhu X (2016) Apigenin suppresses colorectal cancer cell proliferation, migration and invasion via inhibition of the Wnt/β-catenin signaling pathway. Oncol Lett 11(5):3075–3080

    PubMed  PubMed Central  CAS  Google Scholar 

  264. Park S, Gwak J, Han SJ, Oh S (2013) Cardamonin suppresses the proliferation of colon cancer cells by promoting β-catenin degradation. Biol Pharm Bull 13:00158. https://doi.org/10.1248/bpb.b13-00158

    Article  Google Scholar 

  265. Shrivastava S, Jeengar MK, Thummuri D, Koval A, Katanaev VL, Marepally S, Naidu VGM (2017) Cardamonin, a chalcone, inhibits human triple negative breast cancer cell invasiveness by downregulation of Wnt/β-catenin signaling cascades and reversal of epithelial–mesenchymal transition. Biofactors 43(2):152–169. https://doi.org/10.1002/biof.1315

    Article  PubMed  CAS  Google Scholar 

  266. Nicolson GL (2014) Mitochondrial dysfunction and chronic disease: treatment with natural supplements. J Integr Med 13(4):35–43

    Google Scholar 

  267. Cai XZ, Wang J, Xiao-Dong L, Wang GL, Liu FN, Cheng MS, Li F (2009) Curcumin suppresses proliferation and invasion in human gastric cancer cells by downregulation of PAK1 activity and cyclin D1 expression. Cancer Biol Ther 8(14):1360–1368. https://doi.org/10.4161/cbt.8.14.8720

    Article  PubMed  CAS  Google Scholar 

  268. Zhang HT, Luo H, Wu J, Lan LB, Fan DH, Zhu KD, Liu HM (2010) Galangin induces apoptosis of hepatocellular carcinoma cells via the mitochondrial pathway. World J Gastroenterol 16(27):3377. https://doi.org/10.3748/wjg.v16.i27.3377

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  269. Şirin N, Elmas L, Seçme M, Dodurga Y (2020) Investigation of possible effects of apigenin, sorafenib and combined applications on apoptosis and cell cycle in hepatocellular cancer cells. Gene 737:144428. https://doi.org/10.1016/j.gene.2020.144428

    Article  PubMed  CAS  Google Scholar 

  270. Gupta S, Afaq F, Mukhtar H (2002) Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Oncogene 21(23):3727–3738

    PubMed  CAS  Google Scholar 

  271. Maeda Y, Takahashi H, Nakai N, Yanagita T, Ando N, Okubo T, Saito K, Shiga K, Hirokawa T, Hara M, Ishiguro H, Matsuo Y, Takiguchi S (2018) Apigenin induces apoptosis by suppressing Bcl-xl and Mcl-1 simultaneously via signal transducer and activator of transcription 3 signaling in colon cancer. Int J Oncol 52(5):1661–1673. https://doi.org/10.3892/ijo.2018.4308

    Article  PubMed  CAS  Google Scholar 

  272. Wang W, Heideman L, Chung CS, Pelling JC, Koehler KJ, Birt DF (2000) Cell-cycle arrest at G2/M and growth inhibition by apigenin in human colon carcinoma cell lines. Mol Carcinog 28(2):102–110

    PubMed  Google Scholar 

  273. Seo HS, Jo JK, Ku JM, Choi HS, Choi YK, Woo JK, Shin YC (2015) Induction of caspase-dependent extrinsic apoptosis by apigenin through inhibition of signal transducer and activator of transcription 3 (STAT3) signalling in HER2-overexpressing BT-474 breast cancer cells. Biosci Rep 35(6):1–14. https://doi.org/10.1042/BSR20150165

    Article  CAS  Google Scholar 

  274. Wang Z, Lu W, Li Y, Tang B (2013) Alpinetin promotes Bax translocation, induces apoptosis through the mitochondrial pathway and arrests human gastric cancer cells at the G2/M phase. Mol Med Rep 7:915–920. https://doi.org/10.3892/mmr.2012.1243

    Article  PubMed  CAS  Google Scholar 

  275. Fan J, Yang X, Bi Z (2015) 6-Gingerol inhibits osteosarcoma cell proliferation through apoptosis and AMPK activation. Tumor Biol 36(2):1135–1141

    CAS  Google Scholar 

  276. Fuzer AM, Martin AC, Becceneri AB, da Silva JA, Vieira PC, Cominetti MR (2019) [10]-Gingerol affects multiple metastatic processes and induces apoptosis in MDAMB-231 breast tumor cells. Anti-cancer Agent Med 19(5):645–654

    CAS  Google Scholar 

  277. Gan H, Zhang Y, Zhou Q, Zheng L, Xie X, Veeraraghavan VP, Mohan SK (2019) Zingerone induced caspase-dependent apoptosis in MCF-7 cells and prevents 7, 12-dimethylbenz (a) anthracene-induced mammary carcinogenesis in experimental rats. J Biochem Mol Toxicol 33(10):e22387. https://doi.org/10.1002/jbt.22387

    Article  PubMed  CAS  Google Scholar 

  278. Hu R, Zhou P, Peng YB, Xu X, Ma J, Liu Q, Li P (2012) 6-Shogaol induces apoptosis in human hepatocellular carcinoma cells and exhibits anti-tumor activity in vivo through endoplasmic reticulum stress. PLoS One 7(6):e39664. https://doi.org/10.1371/journal.pone.0039664

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  279. Tan BS, Kang O, Mai CW, Tiong KH, Khoo ASB, Pichika MR, Leong CO (2013) 6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor γ (PPARγ). Cancer Lett 336(1):127–139. https://doi.org/10.1016/j.canlet.2013.04.014

    Article  PubMed  CAS  Google Scholar 

  280. Shyanti RK, Sehrawat A, Singh SV, Mishra JPN, Singh RP (2017) Zerumbone modulates CD1d expression and lipid antigen presentation pathway in breast cancer cells. Toxicol In Vitro 44:74–84

    PubMed  CAS  Google Scholar 

  281. Liao W, Chen L, Ma X, Jiao R, Li X, Wang Y (2016) Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells. Eur J Med Chem 114:24–32

    PubMed  CAS  Google Scholar 

  282. Choi JB, Kim JH, Lee H, Pak JN, Shim BS, Kim SH (2018) Reactive oxygen species and p53 mediated activation of p38 and caspases is critically involved in kaempferol induced apoptosis in colorectal cancer cells. J Agric Food Chem 66(38):9960–9967

    PubMed  CAS  Google Scholar 

  283. Halimah E, Diantini A, Destiani DP, Pradipta IS, Sastramihardja HS, Lestari K, Koyama H (2015) Induction of caspase cascade pathway by kaempferol-3-O-rhamnoside in LNCaP prostate cancer cell lines. Biomed Rep 3(1):115–117

    PubMed  Google Scholar 

  284. Tu LY, Bai HH, Cai JY, Deng SP (2016) The mechanism of kaempferol induced apoptosis and inhibited proliferation in human cervical cancer SiHa cell: From macro to nano. Scanning 38(6):644–653. https://doi.org/10.1002/sca.21312

    Article  PubMed  CAS  Google Scholar 

  285. Su L, Chen X, Wu J, Lin B, Zhang H, Lan L, Luo H (2013) Galangin inhibits proliferation of hepatocellular carcinoma cells by inducing endoplasmic reticulum stress. Food Chem Toxicol 62:810–816. https://doi.org/10.1016/j.fct.2013.10.019

    Article  PubMed  CAS  Google Scholar 

  286. Chan ML, Liang JW, Hsu LC, Chang WL, Lee SS, Guh JH (2015) Zerumbone, a ginger sesquiterpene, induces apoptosis and autophagy in human hormone-refractory prostate cancers through tubulin binding and crosstalk between endoplasmic reticulum stress and mitochondrial insult. Naunyn Schmiedeberg’s Arch Pharmacol 388(11):1223–1236

    CAS  Google Scholar 

  287. Guo H, Lin W, Zhang X, Zhang X, Hu Z, Li L, Ren F (2017) Kaempferol induces hepatocellular carcinoma cell death via endoplasmic reticulum stress-CHOP-autophagy signaling pathway. Oncotarget 8(47):82207

    PubMed  PubMed Central  Google Scholar 

  288. Yue Z, Jin S, Yang C, Levine AJ, Heintz N (2003) Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A 100:15077–15082

    PubMed  PubMed Central  CAS  Google Scholar 

  289. Ren K, Zhang W, Wu G, Ren J, Lu H, Li Z, Han X (2016) Synergistic anti-cancer effects of galangin and berberine through apoptosis induction and proliferation inhibition in oesophageal carcinoma cells. Biomed Pharmacother 84:1748–1759

    PubMed  CAS  Google Scholar 

  290. Li X, Wang Y, Xiong Y, Wu J, Ding H, Chen X, Zhang H (2016) Galangin induces autophagy via deacetylation of LC3 by SIRT1 in HepG2 Cells. Sci Rep 6:30496. https://doi.org/10.1038/srep30496

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  291. Cao X, Liu B, Cao W, Zhang W (2013) Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells. Chin J Cancer Res 25(2):212–222. https://doi.org/10.3978/j.issn.1000-9604.2013.04.01

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  292. Lee Y, Sung B, Kang YJ, Kim DH, Jang J, Hwang SY, Kim ND (2014) Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells. Int J Oncol 44:1599–1606. https://doi.org/10.3892/ijo.2014.2339

    Article  PubMed  CAS  Google Scholar 

  293. Wang B, Zhao XH (2017) Apigenin induces both intrinsic and extrinsic pathways of apoptosis in human colon carcinoma HCT-116 cells. Oncol Rep 37(2):1132–1140

    PubMed  CAS  Google Scholar 

  294. Czarnik-Kwaśniak J, Kwaśniak K, Kwasek P, Świerzowska E, Strojewska A, Tabarkiewicz J (2020) The influence of lycopene,[6]-gingerol, and silymarin on the apoptosis on U-118MG glioblastoma cells in vitro model. Nutrients 12(1):96

    Google Scholar 

  295. Luna-Dulcey L, Tomasin R, Naves MA, da Silva JA, Cominetti MR (2018) Autophagy-dependent apoptosis is triggered by a semi-synthetic [6]-gingerol analogue in triple negative breast cancer cells. Oncotarget 9(56):30787

    PubMed  PubMed Central  Google Scholar 

  296. Ko H, Kim YJ, Amor EC, Lee JW, Kim HC, Kim HJ, Yang HO (2011) Induction of autophagy by dimethyl cardamonin is associated with proliferative arrest in human colorectal carcinoma HCT116 and LOVO cells. J Cell Biochem 112(9):2471–2479. https://doi.org/10.1002/jcb.23171

    Article  PubMed  CAS  Google Scholar 

  297. Jegannathan SD, Arul S, Dayalan H (2016) Zerumbone, a sesquiterpene, controls proliferation and induces cell cycle arrest in human laryngeal carcinoma cell line Hep-2. Nutr Cancer 68(5):865–872. https://doi.org/10.1080/01635581.2016.1159701

    Article  PubMed  CAS  Google Scholar 

  298. Du J, Tang B, Wang J, Sui H, Jin X (2012) Antiproliferative effect of alpinetin in BxPC-3 pancreatic cancer cells. Int J Mol Med 29:607–612. https://doi.org/10.3892/ijmm.2012.884

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  299. Sahu RP, Batra S, Srivastava SK (2009) Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells. Br J Cancer 100(9):1425. https://doi.org/10.1038/sj.bjc.6605039

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  300. Wei W, Azhar Rasul AS, Sarfraz I, Hussain G, Nageen B, Liu X, Li J (2019) Curcumol: from plant roots to cancer roots. Int J Biol Sci 15(8):1600–1609. https://doi.org/10.7150/ijbs.34716

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  301. Yan X, Qi M, Li P, Zhan Y, Shao H (2017) Apigenin in cancer therapy: anti-cancer effects and mechanisms of action. Cell Biosci 7(1):50

    PubMed  PubMed Central  Google Scholar 

  302. Tseng TH, Chien MH, Lin WL, Wen YC, Chow JM, Chen CK, Lee WJ (2017) Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression. Environ Toxicol 32(2):434–444. https://doi.org/10.1002/tox.2224

    Article  PubMed  CAS  Google Scholar 

  303. Lee SH, Cekanova M, Baek SJ (2008) Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells. Mol Carcinog 47(3):197–208. https://doi.org/10.1002/mc.20374

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  304. Yagihashi S, Miura Y, Yagasaki K (2008) Inhibitory effect of gingerol on the proliferation and invasion of hepatoma cells in culture. Cytotechnology 57(2):129–136. https://doi.org/10.1007/s10616-008-9121-8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  305. Lin CB, Lin CC, Tsay GJ (2012) 6-Gingerol inhibits growth of colon cancer cell LoVo via induction of G2/M arrest. Evid Based Complementary Alternate Med 2012:1–7. https://doi.org/10.1155/2012/326096

    Article  Google Scholar 

  306. Park YJ, Wen J, Bang S, Park SW, Song SY (2006) [6]-Gingerol induces cell cycle arrest and cell death of mutant p53-expressing pancreatic cancer cells. Yonsei Med J 47(5):688–697

    PubMed  PubMed Central  CAS  Google Scholar 

  307. Rasmussen A, Murphy K, Hoskin DW (2019) 10-Gingerol inhibits ovarian cancer cell growth by inducing G2 arrest. Adv Pharm Bull. https://doi.org/10.15171/apb.2019.080

  308. Abdul AB, Abdelwahab SI, Jalinas JB, Al-Zubairi AS, Taha MME (2009) Combination of zerumbone and cisplatin to treat cervical intraepithelial neoplasia in female BALB/c mice. Int J Gynecol Cancer 19(6):1004–1010

    PubMed  Google Scholar 

  309. Wang D, Li Y, Cui P, Zhao Q, Tan BB, Zhang ZD, Jia N (2016) Zerumbone induces gastric cancer cells apoptosis: Involving cyclophilin A. Biomed Pharmacother 83:740–745. https://doi.org/10.1016/j.biopha.2016.07.034

    Article  PubMed  CAS  Google Scholar 

  310. Ma S, Lei Y, Zhang L, Wang J (2018) Effects of zerumbone on proliferation and apoptosis of esophageal cancer cells and on P53 and Bcl-2 expression levels. Oncol Lett 16(4):4379–4383

    PubMed  PubMed Central  Google Scholar 

  311. Kannan M, Jayamohan S, Mohanakumar AK, Moorthy RK, Purushothama KM, Arockiam AJV (2019) Bcl-2/BCL2L12 mediated apoptosis and cell cycle arrest induced by Kaempferol through the suppression of PI3K/AKT signaling pathway in Hepatocellular carcinoma. J Adv Appl Sci Res 2(1):2454–3225

    Google Scholar 

  312. Parmar F, Patel C, Highland H, Pandya H, George LB (2016) Antiproliferative efficacy of kaempferol on cultured Daudi cells: an in silico and in vitro study. Adv Biol 2016:1–10. https://doi.org/10.1155/2016/9521756

    Article  CAS  Google Scholar 

  313. Choi JS, Ryu J, Bae WY, Park A, Nam S, Kim JE, Jeong JW (2018) Zingerone suppresses tumor development through decreasing cyclin D1 expression and inducing mitotic arrest. Int J Mol Sci 19(9):2832. https://doi.org/10.3390/ijms19092832

    Article  PubMed Central  CAS  Google Scholar 

  314. Malami I, Abdul AB, Abdullah R, Kassim NK, Rosli R (2017) Crude extracts, flavokawain B and alpinetin compounds from the Rhizome of Alpinia mutica induce cell death via UCK2 enzyme inhibition and in turn reduce 18S rRNA biosynthesis in HT-29 cells. PLoS One 12:e0170233. https://doi.org/10.1371/journal.pone.0170233

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  315. Zhang L, Cheng X, Gao Y, Zhang C, Bao J, Guan (2016) Curcumin inhibits metastasis in human papillary thyroid carcinoma BCPAP cells via down-regulation of the TGF-β/Smad2/3 signaling pathway. Exp Cell Res 341(2):157–165. https://doi.org/10.1016/j.yexcr.2016.01.00

    Article  PubMed  CAS  Google Scholar 

  316. Choi YJ, Lee YH, Lee ST (2015) Galangin and kaempferol suppress phorbol-12-myristate-13-acetate-induced matrix metalloproteinase-9 expression in human fibrosarcoma HT-1080 cells. Mol Cells 38(2):151–155

    PubMed  Google Scholar 

  317. Cao J, Wang H, Chen F, Fang J, Xu A, Xi W, Wang Z (2016) Galangin inhibits cell invasion by suppressing the epithelial-mesenchymal transition and inducing apoptosis in renal cell carcinoma. Mol Med Rep 13(5):4238–4244

    PubMed  PubMed Central  CAS  Google Scholar 

  318. Zhu Y, Rao Q, Zhang X, Zhou X (2018) Galangin induced antitumor effects in human kidney tumor cells mediated via mitochondrial mediated apoptosis, inhibition of cell migration and invasion and targeting PI3K/AKT/mTOR signalling pathway. J BUON 23(3):795–799

    PubMed  Google Scholar 

  319. Cao HH, Chu JH, Kwan HY, Su T, Yu H, Cheng CY, Chou GX (2016) Inhibition of the STAT3 signaling pathway contributes to apigenin-mediated anti-metastatic effect in melanoma. Sci Rep 6:21731

    PubMed  PubMed Central  CAS  Google Scholar 

  320. Hu XW, Meng D, Fang J (2008) Apigenin inhibited migration and invasion of human ovarian cancer A2780 cells through focal adhesion kinase. Carcinogenesis 29(12):2369–2376

    PubMed  CAS  Google Scholar 

  321. Chunhua L, Donglan L, Xiuqiong F, Lihua Z, Qin F, Yawei L, Liang Z, Ge W, Linlin J, Ping Z, Kun L, Xuegang S (2013) Apigenin up-regulates transgelin and inhibits invasion and migration of colorectal cancer through decreased phosphorylation of AKT. J Nutr Biochem 24:1766–1775

    PubMed  Google Scholar 

  322. Tang B, Du J, Wang J, Tan G, Gao Z (2012) Alpinetin suppresses proliferation of human hepatoma cells by the activation of MKK7 and elevates sensitization to cis-diammined dichloridoplatium. Oncol Rep 27:1090–1096. https://doi.org/10.3892/or.2011.1580

    Article  PubMed  CAS  Google Scholar 

  323. Hosseini N, Khoshnazar A, Saidijam M, Azizi Jalilian F, Najafi R, Mahdavinezhad A, Amini R (2019) Zerumbone suppresses human colorectal cancer invasion and metastasis via modulation of FAk/PI3k/NFκB-uPA pathway. Nutr Cancer 71(1):159–171. https://doi.org/10.1080/01635581.2018.1540719

    Article  PubMed  Google Scholar 

  324. Wani NA, Zhang B, Teng KY, Barajas JM, Motiwala T, Hu P, Jacob ST (2018) Reprograming of glucose metabolism by zerumbone suppresses hepatocarcinogenesis. Mol Cancer Res 16(2):256–268

    PubMed  CAS  Google Scholar 

  325. Abdelwahab SI, Abdul AB, Zain ZNM, Hadi AHA (2012) Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells. Int Immunopharmacol 12(4):594–602

    PubMed  CAS  Google Scholar 

  326. Kim S, Lee J, Jeon M, Lee JE, Nam SJ (2016) Zerumbone suppresses the motility and tumorigenicity of triple negative breast cancer cells via the inhibition of TGF-β1 signaling pathway. Oncotarget 7(2):1544–1558

    PubMed  Google Scholar 

  327. Phromnoi K, Yodkeeree S, Anuchapreeda S, Limtrakul P (2009) Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids. Acta Pharmacol Sin 30(8):1169–1176

    PubMed  PubMed Central  CAS  Google Scholar 

  328. Li S, Yan T, Deng R, Jiang X, Xiong H, Wang Y, Zhu Y (2017) Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1. Oncotargets Ther 10:4809. https://doi.org/10.2147/OTT.S140886

    Article  Google Scholar 

  329. Kim JH (2016) Kaempferol inhibits pancreatic cancer cell growth and migration through the blockade of EGFR-related pathway in vitro. PLoS One 11(5):e0155264

    PubMed  PubMed Central  Google Scholar 

  330. Jo E, Park SJ, Choi YS, Jeon WK, Kim BC (2015) Kaempferol suppresses transforming growth factor-β1–induced epithelial-to-mesenchymal transition and migration of A549 lung cancer cells by inhibiting Akt1-mediated phosphorylation of Smad3 at threonine-179. Neoplasia 17(7):525–537. https://doi.org/10.1016/j.neo.2015.06.004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  331. Hang M, Zhao F, Chen SB, Sun Q, Zhang CX (2015) Kaempferol modulates the metastasis of human non-small cell lung cancer cells by inhibiting epithelial-mesenchymal transition. Bangladesh J Pharmacol 10(2):267–270. https://doi.org/10.3329/bjp.v10i2.21739

    Article  Google Scholar 

  332. Kim YJ, Jeon Y, Kim T, Lim WC, Ham J, Park YN, Ko H (2017) Combined treatment with zingerone and its novel derivative synergistically inhibits TGF-β1 induced epithelial-mesenchymal transition, migration and invasion of human hepatocellular carcinoma cells. Bioorg Med Chem 27(4):1081–1088. https://doi.org/10.1016/j.bmcl.2016.12.04

    Article  CAS  Google Scholar 

  333. Chien MH, Lin YW, Wen YC, Yang YC, Hsiao M, Chang JL, Lee WJ (2019) Targeting the SPOCK1-snail/slug axis-mediated epithelial-to-mesenchymal transition by apigenin contributes to repression of prostate cancer metastasis. J Exp Clin Cancer Res 38(1):246. https://doi.org/10.1186/s13046-019-1247-3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  334. Zhong W, Yang W, Qin Y, Gu W, Xue Y, Tang Y, Sun B (2019) 6-Gingerol stabilized the p-VEGFR2/VE-cadherin/β-catenin/actin complex promotes microvessel normalization and suppresses tumor progression. J Exp Clin Cancer Res 38(1):285

    PubMed  PubMed Central  Google Scholar 

  335. Jeong CH, Bode AM, Pugliese A, Cho YY, Kim HG, Shim JH, Dong Z (2009) [6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase. Cancer Res 69(13):5584–5591

    PubMed  CAS  Google Scholar 

  336. Krause M, Dubrovska A, Linge A, Baumann M (2017) Cancer stem cells: radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments. Adv Drug Deliv 109:63–73

    CAS  Google Scholar 

  337. Tang AQ, Cao XC, Tian L, He L, Liu F (2015) Apigenin inhibits the self-renewal capacity of human ovarian cancer SKOV3derived sphere-forming cells. Mol Med Rep 11:2221–2136

    PubMed  CAS  Google Scholar 

  338. Liu J, Cao XC, Xiao Q, Quan MF (2015) Apigenin inhibits HeLa sphere forming cells through inactivation of casein kinase 2α. Mol Med Rep 11(1):665–669

    PubMed  CAS  Google Scholar 

  339. Das PK, Zahan T, Abdur MR, Khanam JA, Pillai S, Islam F (2019) Natural compounds targeting cancer stem cells: a promising resource for chemotherapy. Anti Cancer Agents Med Chem 19(15):1796–1808

    CAS  Google Scholar 

  340. Mahoney KM, Rennert PD, Freeman GJ (2015) Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov 14:561–584

    PubMed  CAS  Google Scholar 

  341. Mishra AK, Kadoishi T, Wang X, Driver E, Chen Z, Wang XJ, Wang JH (2016) Squamous cell carcinomas escape immune surveillance via inducing chronic activation and exhaustion of CD8+ T Cells co-expressing PD-1 and LAG-3 inhibitory receptors. Oncotarget 7:81341–81356

    PubMed  PubMed Central  Google Scholar 

  342. Nelson N, Szekeres K, Iclozan C, Rivera IO, McGill A, Johnson G, Ghansah T (2017) Apigenin: selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine pancreatic cancer. PLoS One 12(2):e0170197. https://doi.org/10.1371/journal.pone.0170197

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  343. Jiang BH, Qiu JG, Wang L, Liu WJ, Wang JF, Zhao EJ, Wang W (2019) Apigenin inhibits IL-6 transcription and suppresses esophageal carcinogenesis. Front Pharmacol 10:1002. https://doi.org/10.3389/fphar.2019.01002

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Plant Molecular Cytogenetics Laboratory, Centre of Advanced Study, Department of Botany, Ballygunge Science College, University of Calcutta, Kolkata, India

    Indrani Manna, Debalina Das, Sejuty Mondal & Maumita Bandyopadhyay

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  2. Debalina Das
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  1. SD College, Barnala, Punjab, India

    Manish Kumar

  2. Chandigarh University, Mohali, Punjab, India

    Ashita Sharma

  3. Technion – Israel Institute of Technology, Technion City, Haifa, Israel

    Praveen Kumar

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Manna, I., Das, D., Mondal, S., Bandyopadhyay, M. (2020). Potential Pharmacotherapeutic Phytochemicals from Zingiberaceae for Cancer Prevention. In: Kumar, M., Sharma, A., Kumar, P. (eds) Pharmacotherapeutic Botanicals for Cancer Chemoprevention . Springer, Singapore. https://doi.org/10.1007/978-981-15-5999-0_10

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