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Polyphenols as Modulators of Oxidative Stress in Cancer Disease

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Polyphenols-based Nanotherapeutics for Cancer Management

Abstract

Epidemiologic reports have revealed that cancer is a major health risk and considered a leading cause of increasing death rates all over the world. High oxidative stress can mediate chronic diseases such as onset of cancer because of damaging effects on vital molecules, DNA mutation, cell proliferation, and genome modification. Among bioactive phytoconstituents, dietary polyphenols are widely distributed in fruits, vegetables, spices, etc., having strong antioxidant activity and believed to act extensively as chemopreventive agents causing interference with carcinogenesis. Anticancer effect of polyphenols is induced via regulation of antioxidant enzymatic activity, apoptosis induction by downregulation of various signaling pathways, and cell cycle arrest by initiating cell senescence associated with oxidative stress. Several polyphenols are demonstrated to act directly by affecting epigenetic process via modulating level of oxidative stress and reactive oxygen species (ROS) generation. Additionally, prooxidant mechanism of polyphenols impedes the metabolic process of cancer stem cells as well as self-renewal signaling pathways. Polyphenols can be suggested as a beneficial anticancer tool in a combinational protocol with a standard chemotherapeutic agent resulting in significantly fewer side effects.

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References

  1. Rizeq B, Gupta I, Ilesanmi J, AlSafran M, Rahman MDM, Ouhtit A. The power of phytochemicals combination in cancer chemoprevention. J Cancer. 2020;11:4521–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Pitot HC. The molecular biology of carcinogenesis. Cancer. 1993;72:962–70.

    Article  CAS  PubMed  Google Scholar 

  3. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49:1603–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kawasaki BT, Hurt EM, Mistree T, Farrar WL. Targeting cancer stem cells with phytochemicals. Mol Interv. 2008;8:174–84.

    Article  CAS  PubMed  Google Scholar 

  5. Stepanic V, Gasparovic A, Troselj K, Amic D, Zarkovic N. Selected attributes of polyphenols in targeting oxidative stress in cancer. Curr Top Med Chem. 2015;15:496–509.

    Article  CAS  PubMed  Google Scholar 

  6. Pignatti F, Jonsson B, Blumenthal G, Justice R. Assessment of benefits and risks in development of targeted therapies for cancer - The view of regulatory authorities. Mol Oncol. 2015;9:1034–41.

    Article  PubMed  Google Scholar 

  7. Maraldi T. Natural compounds as modulators of NADPH oxidases. Oxid Med Cell Longev. 2013;2013:271602.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: Current state. Nutr J. 2016;15:71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Kalaiselvan I, Samuthirapandi M, Govindaraju A, Sheeja Malar D, Kasi PD. Olive oil and its phenolic compounds (hydroxytyrosol and tyrosol) ameliorated TCDD-induced hepatotoxicity in rats via inhibition of oxidative stress and apoptosis. Pharm Biol. 2016;54:338–46.

    Article  CAS  PubMed  Google Scholar 

  10. León-González AJ, Auger C, Schini-Kerth VB. Pro-oxidant activity of polyphenols and its implication on cancer chemoprevention and chemotherapy. Biochem Pharmacol. 2015;98:371–80.

    Article  PubMed  CAS  Google Scholar 

  11. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxidants Redox Signal. 2014;20:1126–67.

    Article  CAS  Google Scholar 

  12. Aggarwal V, Tuli HS, Varol A, Thakral F, Yerer MB, Sak K, et al. Role of reactive oxygen species in cancer progression: molecular mechanisms and recent advancements. Biomolecules. 2019;9:735.

    Article  CAS  PubMed Central  Google Scholar 

  13. Vittorio O, Curcio M, Cojoc M, Goya GF, Hampel S, Iemma F, et al. Polyphenols delivery by polymeric materials: challenges in cancer treatment. Drug Deliv. 2017;24:162–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Park E-J, M. Pezzuto J. Flavonoids in cancer prevention. Anticancer Agents Med Chem. 2012;12:836–51.

    Article  CAS  PubMed  Google Scholar 

  15. Zubair H, Khan HY, Sohail A, Azim S, Ullah MF, Ahmad A, et al. Redox cycling of endogenous copper by thymoquinone leads to ROS-mediated DNA breakage and consequent cell death: Putative anticancer mechanism of antioxidants. Cell Death Dis. 2013;4:e660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Margalioth EJ, Schenker JG, Chevion M. Copper and zinc levels in normal and malignant tissues. Cancer. 1983;52:868–72.

    Article  CAS  PubMed  Google Scholar 

  17. Khan HY, Zubair H, Faisal M, Ullah MF, Farhan M, Sarkar FH, et al. Plant polyphenol induced cell death in human cancer cells involves mobilization of intracellular copper ions and reactive oxygen species generation: a mechanism for cancer chemopreventive action. Mol Nutr Food Res. 2014;58:437–46.

    Article  CAS  PubMed  Google Scholar 

  18. Betteridge DJ. What is oxidative stress? Metabolism. 2000;49:3–8.

    Article  CAS  PubMed  Google Scholar 

  19. Klaunig JE, Wang Z. Oxidative stress in carcinogenesis. Curr Opin Toxicol. 2018;7:116–21.

    Article  Google Scholar 

  20. Little MP, Heidenreich WF, Moolgavkar SH, Schöllnberger H, Thomas DC. Systems biological and mechanistic modelling of radiation-induced cancer. Radiat Environ Biophys. 2008;47:39–47.

    Article  CAS  PubMed  Google Scholar 

  21. Klaunig JE, Kamendulis LM, Hocevar BA. Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol. 2010;38:96–109.

    Article  CAS  PubMed  Google Scholar 

  22. Sosa V, Moliné T, Somoza R, Paciucci R, Kondoh H, LLeonart ME. Oxidative stress and cancer: an overview. Ageing Res Rev. 2013;12:376–90.

    Article  CAS  PubMed  Google Scholar 

  23. Guina T, Biasi F, Calfapietra S, Nano M, Poli G. Inflammatory and redox reactions in colorectal carcinogenesis. Ann N Y Acad Sci. 2015;1340:95–103.

    Article  CAS  PubMed  Google Scholar 

  24. Thapa D, Ghosh R. Chronic inflammatory mediators enhance prostate cancer development and progression. Biochem Pharmacol. 2015;94:53–62.

    Article  CAS  PubMed  Google Scholar 

  25. Murata M, Thanan R, Ma N, Kawanishi S. Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis. J Biomed Biotechnol. 2012;2012:623019.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Huo L, Li CW, Huang TH, Lam YC, Xia W, Tu C, et al. Activation of keap1/nrf2 signaling pathway by nuclear epidermal growth factor receptor in cancer cells. Am J Transl Res. 2014;6:649–63.

    PubMed  PubMed Central  Google Scholar 

  27. Korbecki J, Baranowska-Bosiacka I, Gutowska I, Chlubek D. The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid. J Physiol Pharmacol. 2013;64:409–21.

    CAS  PubMed  Google Scholar 

  28. Wiemer EAC. Stressed tumor cell, chemosensitized cancer. Nat Med. 2011;17:1552–4.

    Article  CAS  PubMed  Google Scholar 

  29. Barrera G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol. 2012;2012:137289.

    PubMed  PubMed Central  Google Scholar 

  30. Brigelius-Flohé R, Kipp A. Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta. 1790;2009:1555–68.

    Google Scholar 

  31. Malik UU, Siddiqui IA, Hashim Z, Zarina S. Measurement of serum paraoxonase activity and MDA concentrations in patients suffering with oral squamous cell carcinoma. Clin Chim Acta. 2014;430:38–42.

    Article  CAS  PubMed  Google Scholar 

  32. Spencer CM, Faulds D. Paclitaxel: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer. Drugs. 1994;48:794–847.

    Article  CAS  PubMed  Google Scholar 

  33. Bekaii-Saab T, Kim R, Kim TW, O’Connor JM, Strickler JH, Malka D, et al. Third- or later-line therapy for metastatic colorectal cancer: reviewing best practice. Clin. Colorectal Cancer. 2019;18:e117–29.

    Article  PubMed  Google Scholar 

  34. Mentella MC, Scaldaferri F, Ricci C, Gasbarrini A, Miggiano GAD. Cancer and mediterranean diet: a review. Nutrients. 2019;11:2059.

    Article  PubMed Central  Google Scholar 

  35. Schwingshackl L, Schwedhelm C, Galbete C, Hoffmann G. Adherence to mediterranean diet and risk of cancer: an updated systematic review and meta-analysis. Nutrients. 2017;9:1063.

    Article  PubMed Central  CAS  Google Scholar 

  36. Wang K, Karin M. Tumor-elicited inflammation and colorectal cancer. Adv Cancer Res. 2015;128:173–96.

    Article  CAS  PubMed  Google Scholar 

  37. Schetter AJ, Heegaard NHH, Harris CC. Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis. 2009;31:37–49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Dmitrieva OS, Shilovskiy IP, Khaitov MR, Grivennikov SI. Interleukins 1 and 6 as main mediators of inflammation and cancer. Biochem. 2016;81:166–78.

    Google Scholar 

  39. Munn LL. Cancer and inflammation. Wiley Interdiscip Rev Syst Biol Med. 2017;9:e1370.

    Article  CAS  Google Scholar 

  40. Wang D, Dubois RN. Prostaglandins and cancer. Gut. 2006;55:115–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Nourazarian AR, Kangari P, Salmaninejad A. Roles of oxidative stress in the development and progression of breast cancer. Asian Pacific J Cancer Prev. 2014;15:4745–51.

    Article  Google Scholar 

  42. Sies H. What is oxidative stress? J Japan Med Assoc. 2000;45:1–8.

    Google Scholar 

  43. Supic G, Jagodic M, Magic Z. Epigenetics: a new link between nutrition and cancer. Nutr Cancer. 2013;65:781–92.

    Article  CAS  PubMed  Google Scholar 

  44. Sandoval J, Esteller M. Cancer epigenomics: beyond genomics. Curr Opin Genet Dev. 2012;22:50–5.

    Article  CAS  PubMed  Google Scholar 

  45. Baxter E, Windloch K, Gannon F, Lee JS. Epigenetic regulation in cancer progression. Cell Biosci. 2014;4:45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Wajed SA, Laird PW, DeMeester TR. DNA methylation: an alternative pathway to cancer. Ann Surg. 2001;234:10–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Shanmugam MK, Sethi G. Role of epigenetics in inflammation-associated diseases. Subcell Biochem. 2013;61:627–57.

    Article  CAS  PubMed  Google Scholar 

  48. Cheung HH, Lee TL, Rennert OM, Chan WY. DNA methylation of cancer genome. Birth Defects Res C Embryo Today Rev. 2009;87:335–50.

    Article  CAS  Google Scholar 

  49. Olzscha H, Sheikh S, La Thangue NB. Deacetylation of chromatin and gene expression regulation: a new target for epigenetic therapy. Crit Rev Oncog. 2015;20:1–17.

    Article  PubMed  Google Scholar 

  50. Figueroa-González G, Pérez-Plasencia C. Strategies for the evaluation of DNA damage and repair mechanisms in cancer. Oncol Lett. 2017;13:3982–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Van Houten B, Cheng S, Chen Y. Measuring gene-specific nucleotide excision repair in human cells using quantitative amplification of long targets from nanogram quantities of DNA. Mutat Res. 2000;460:81–94.

    Article  PubMed  Google Scholar 

  52. Strauss EC, Orkin SH. Guanine-adenine ligation-mediated PCR in vivo footprinting. Methods. 1997;11:164–70.

    Article  CAS  PubMed  Google Scholar 

  53. Wang G, Hallberg LM, Englander EW. Rapid SINE-mediated detection of cisplatin:DNA adduct formation in vitro and in vivo in blood. Mutat Res. 1999;434:67–74.

    Article  CAS  PubMed  Google Scholar 

  54. Collins AR. Measuring oxidative damage to DNA and its repair with the comet assay. Biochim Biophys Acta. 1840;2014:794–800.

    Google Scholar 

  55. Collins AR, Azqueta A. DNA repair as a biomarker in human biomonitoring studies; further applications of the comet assay. Mutat Res. 2012;736:122–9.

    Article  CAS  PubMed  Google Scholar 

  56. Glei M, Hovhannisyan G, Pool-Zobel BL. Use of Comet-FISH in the study of DNA damage and repair: review. Mutat Res. 2009;681:33–43.

    Article  CAS  PubMed  Google Scholar 

  57. Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol. 2004;26:249–61.

    Article  CAS  PubMed  Google Scholar 

  58. Collins AR, Azqueta A. single-cell gel electrophoresis combined with lesion-specific enzymes to measure oxidative damage to DNA. In: Conn PM, editor. Methods in cell biology. Cambridge, MA: Academic Press; 2012. p. 69–92.

    Chapter  Google Scholar 

  59. Kumari S, Rastogi R, Singh K, Singh S, Sinha R. DNA damage: detection strategies. Excli J. 2008;7:44–62.

    Google Scholar 

  60. Berton TR, Mitchell DL. Quantification of DNA photoproducts in mammalian cell DNA using radioimmunoassay. Methods Mol Biol. 2012;920:177–87.

    Article  CAS  PubMed  Google Scholar 

  61. Santella RM. Immunological methods for detection of carcinogen-DNA damage in humans. Cancer Epidemiol Biomarkers Prev. 1999;8:733–9.

    CAS  PubMed  Google Scholar 

  62. Yatabe Y. ALK FISH and IHC: You cannot have one without the other. J Thorac Oncol. 2015;10:548–50.

    Article  PubMed  Google Scholar 

  63. Kriste AG, Martincigh BS, Salter LF. A sensitive immunoassay technique for thymine dimer quantitation in UV-irradiated DNA. J Photochem Photobiol A Chem. 1996;93:185–92.

    Article  CAS  Google Scholar 

  64. Mullins EA, Rubinson EH, Pereira KN, Calcutt MW, Christov PP, Eichman BF. An HPLC-tandem mass spectrometry method for simultaneous detection of alkylated base excision repair products. Methods. 2013;64:59–66.

    Article  CAS  PubMed  Google Scholar 

  65. Caldecott KW. DNA single-strand break repair. Exp Cell Res. 2014;329:2–8.

    Article  CAS  PubMed  Google Scholar 

  66. Cadet J, Douki T, Frelon S, Sauvaigo S, Pouget JP, Ravanat JL. Assessment of oxidative base damage to isolated and cellular DNA by HPLC-MS/MS measurement. Free Radic Biol Med. 2002;33:441–9.

    Article  CAS  PubMed  Google Scholar 

  67. Pouget JP, Douki T, Richard MJ, Cadet J. DNA damage induced in cells by γ and UVA radiation as measured by HPLC/GC-MS and HPLC-EC and comet assay. Chem Res Toxicol. 2000;13:541–9.

    Article  CAS  PubMed  Google Scholar 

  68. Fojta M, Daňhel A, Havran L, Vyskočil V. Recent progress in electrochemical sensors and assays for DNA damage and repair. Trends Anal Chem. 2016;79:160–7.

    Article  CAS  Google Scholar 

  69. Boon EM, Ceres DM, Drummond TG, Hill MG, Barton JK. Mutation detection by electrocatalysis at DNA-modified electrodes. Nat Biotechnol. 2000;18:1096–100.

    Article  CAS  PubMed  Google Scholar 

  70. Hail N, Cortes M, Drake EN, Spallholz JE. Cancer chemoprevention: a radical perspective. Free Radic Biol Med. 2008;45:97–110.

    Article  CAS  PubMed  Google Scholar 

  71. Lambert JD, Elias RJ. The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention. Arch Biochem Biophys. 2010;501:65–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Yadav E, Singh D, Yadav P, Verma A. Attenuation of dermal wounds via downregulating oxidative stress and inflammatory markers by protocatechuic acid rich n-butanol fraction of Trianthema portulacastrum Linn. in wistar albino rats. Biomed Pharmacother. 2017;96:86–97.

    Article  CAS  PubMed  Google Scholar 

  73. Yadav E, Singh D, Yadav P, Verma A. Ameliorative effect of biofabricated ZnO nanoparticles of: Trianthema portulacastrum Linn. on dermal wounds via removal of oxidative stress and inflammation. RSC Adv. 2018;8:21621–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Yadav E, Singh D, Debnath B, Rathee P, Yadav P, Verma A. Molecular docking and cognitive impairment attenuating effect of phenolic compound rich fraction of trianthema portulacastrum in scopolamine induced Alzheimer’s disease like condition. Neurochem Res. 2019;44:1665–77.

    Article  CAS  PubMed  Google Scholar 

  75. Dai J, Mumper RJ. Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules. 2010;15:7313–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Rahman I, Chung S. Dietary polyphenols, deacetylases and chromatin remodeling in inflammation. J Nutrigenet Nutrigenomics. 2010;3:220–30.

    Article  PubMed  Google Scholar 

  77. Yang P, He X, Malhotra A. Epigenetic targets of polyphenols in cancer. J Environ Pathol Toxicol Oncol. 2014;33:159–65.

    Article  CAS  PubMed  Google Scholar 

  78. Gerhauser C. Cancer chemoprevention and nutri-epigenetics: state of the art and future challenges. In: Pezzuto JM, Suh N, editors. Natural products in cancer prevention and therapy. Topics in current chemistry. Berlin: Springer; 2012. p. 73–132.

    Chapter  Google Scholar 

  79. Hardy TM, Tollefsbol TO. Epigenetic diet: impact on the epigenome and cancer. Epigenomics. 2011;3:503–18.

    Article  CAS  PubMed  Google Scholar 

  80. Shankar S, Kumar D, Srivastava RK. Epigenetic modifications by dietary phytochemicals: implications for personalized nutrition. Pharmacol Ther. 2013;138:1–17.

    Article  CAS  PubMed  Google Scholar 

  81. Baylin SB, Jones PA. Epigenetic determinants of cancer. Cold Spring Harb Perspect Biol. 2016;8:a019505.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Gonzalez H, Hagerling C, Werb Z. Roles of the immune system in cancer: From tumor initiation to metastatic progression. Genes Dev. 2018;32:1267–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Vanden BW. Epigenetic impact of dietary polyphenols in cancer chemoprevention: lifelong remodeling of our epigenomes. Pharmacol Res. 2012;65:565–76.

    Article  CAS  Google Scholar 

  84. Biswas S, Rahman I. Modulation of steroid activity in chronic inflammation: a novel anti-inflammatory role for curcumin. Mol Nutr Food Res. 2008;52:987–94.

    Article  CAS  PubMed  Google Scholar 

  85. Hassan FU, Rehman MSU, Khan MS, Ali MA, Javed A, Nawaz A, et al. Curcumin as an alternative epigenetic modulator: mechanism of action and potential effects. Front Genet. 2019;10:514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Rahman I. Dietary polyphenols mediated regulation of oxidative stress and chromatin remodeling in inflammation. Nutr Rev. 2008;66:S42–5.

    Article  PubMed  Google Scholar 

  87. Elangovan V, Sekar N, Govindasamy S. Chemopreventive potential of dietary bioflavonoids against 20-methylcholanthrene-induced tumorigenesis. Cancer Lett. 1994;87:107–13.

    Article  CAS  PubMed  Google Scholar 

  88. Tabrez S, Priyadarshini M, Urooj M, Shakil S, Ashraf GM, Khan MS, et al. Cancer chemoprevention by polyphenols and their potential application as nanomedicine. J Environ Sci Heal C Environ Carcinog Ecotoxicol Rev. 2013;31:67–98.

    CAS  Google Scholar 

  89. Camouse MM, Domingo DS, Swain FR, Conrad EP, Matsui MS, Maes D, et al. Topical application of green and white tea extracts provides protection from solar-simulated ultraviolet light in human skin. Exp Dermatol. 2009;18:522–6.

    Article  PubMed  Google Scholar 

  90. Kaur S, Greaves P, Cooke DN, Edwards R, Steward WP, Gescher AJ, et al. Breast cancer prevention by green tea catechins and black tea theaflavins in the C3(1) SV40 T,t antigen transgenic mouse model is accompanied by increased apoptosis and a decrease in oxidative DNA adducts. J Agric Food Chem. 2007;55:3378–85.

    Article  CAS  PubMed  Google Scholar 

  91. Sahnoun Z, Jamoussi K, Mounir ZK. Free radicals: fundamental notions and methods of exploration. Thérapie (Paris). 1997;52:251–70.

    CAS  Google Scholar 

  92. Kundu JK, Surh YJ. Epigallocatechin Gallate inhibits phorbol ester-induced activation of NF-κB and CREB in mouse skin role of p38 MAPK. Ann N Y Acad Sci. 2007;1095:504–12.

    Article  CAS  PubMed  Google Scholar 

  93. Singh BN, Shankar S, Srivastava RK. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol. 2011;82:1807–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Pan H, Chen J, Shen K, Wang X, Wang P, Fu G, et al. Mitochondrial modulation by epigallocatechin 3-gallate ameliorates cisplatin induced renal injury through decreasing oxidative/nitrative stress, inflammation and NF-kB in mice. PLoS One. 2015;10:e0124775.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Thakur VS, Gupta K, Gupta S. Green tea polyphenols causes cell cycle arrest and apoptosis in prostate cancer cells by suppressing class I histone deacetylases. Carcinogenesis. 2012;33:377–84.

    Article  CAS  PubMed  Google Scholar 

  96. Choi KC, Myung GJ, Lee YH, Joo CY, Seung HK, Kang HB, et al. Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation. Cancer Res. 2009;69:583–92.

    Article  CAS  PubMed  Google Scholar 

  97. Nandakumar V, Vaid M, Katiyar SK. (-)-Epigallocatechin-3-gallate reactivates silenced tumor suppressor genes, Cip1/p21 and p16INK4a, by reducing DNA methylation and increasing histones acetylation in human skin cancer cells. Carcinogenesis. 2011;32:537–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Sinha S, Shukla S, Khan S, Tollefsbol TO, Meeran SM. Epigenetic reactivation of p21CIP1/WAF1 and KLOTHO by a combination of bioactive dietary supplements is partially ERα-dependent in ERα-negative human breast cancer cells. Mol Cell Endocrinol. 2015;406:102–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, et al. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 2003;63:7563–70.

    CAS  PubMed  Google Scholar 

  100. Berner C, Aumüller E, Gnauck A, Nestelberger M, Just A, Haslberger AG. Epigenetic control of estrogen receptor expression and tumor suppressor genes is modulated by bioactive food compounds. Ann Nutr Metab. 2011;57:183–9.

    Article  CAS  Google Scholar 

  101. Henning SM, Wang P, Carpenter CL, Heber D. Epigenetic effects of green tea polyphenols in cancer. Epigenomics. 2013;5:729–41.

    Article  CAS  PubMed  Google Scholar 

  102. Lee WJ, Zhu BT. Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. Carcinogenesis. 2006;27:269–77.

    Article  CAS  PubMed  Google Scholar 

  103. Michaluart P, Masferrer JL, Carothers AM, Subbaramaiah K, Zweifel BS, Koboldt C, et al. Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation. Cancer Res. 1999;59:2347–52.

    CAS  PubMed  Google Scholar 

  104. Ozturk G, Ginis Z, Akyol S, Erden G, Gurel A, Akyol O. The anticancer mechanism of caffeic acid phenethyl ester (CAPE): review of melanomas, lung and prostate cancers. Eur Rev Med Pharmacol Sci. 2012;16:2064–8.

    CAS  PubMed  Google Scholar 

  105. Mukhtar H, Ahmad N. Tea polyphenols: prevention of cancer and optimizing health. Am J Clin Nutr. 2000;71:1698S–702S.

    Article  CAS  PubMed  Google Scholar 

  106. Kumar G, Dange P, Kailaje V, Vaidya MM, Ramchandani AG, Maru GB. Polymeric black tea polyphenols modulate the localization and activity of 12-O-tetradecanoylphorbol-13-acetate-mediated kinases in mouse skin: Mechanisms of their anti-tumor-promoting action. Free Radic Biol Med. 2012;53:1358–70.

    Article  CAS  PubMed  Google Scholar 

  107. Mujtaba T, Dou QP. Black tea polyphenols inhibit tumor proteasome activity. In Vivo (Brooklyn). 2012;26:197–202.

    CAS  Google Scholar 

  108. Gorzynik-Debicka M, Przychodzen P, Cappello F, Kuban-Jankowska A, Gammazza AM, Knap N, et al. Potential health benefits of olive oil and plant polyphenols. Int J Mol Sci. 2018;19:686.

    Article  PubMed Central  CAS  Google Scholar 

  109. Wang M, Firrman J, Liu LS, Yam K. A review on flavonoid apigenin: dietary intake, ADME, antimicrobial effects, and interactions with human gut microbiota. Biomed Res Int. 2019;2019:7010467.

    PubMed  PubMed Central  Google Scholar 

  110. Tong X, Pelling J. Targeting the PI3K/Akt/mTOR axis by apigenin for cancer prevention. Anticancer Agents Med Chem. 2013;13:971–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Woo JS, Choo GS, Yoo ES, Kim SH, Lee JH, Han SH, et al. Apigenin induces apoptosis by regulating Akt and MAPK pathways in human melanoma cell A375SM. Mol Med Rep. 2020;22:4877–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Shukla S, Gupta S. Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells. Cell Cycle. 2007;6:1102–14.

    Article  CAS  PubMed  Google Scholar 

  113. Lepley DM, Pelling JC. Induction of p21/WAF1 and G1 cell-cycle arrest by the chemopreventive agent apigenin. Mol Carcinog. 1997;19:74–82.

    Article  CAS  PubMed  Google Scholar 

  114. Choi EJ, Kim GH. Apigenin causes G2/M arrest associated with the modulation of p21Cip1 and Cdc2 and activates p53-dependent apoptosis pathway in human breast cancer SK-BR-3 cells. J Nutr Biochem. 2009;20:285–90.

    Article  CAS  PubMed  Google Scholar 

  115. Gao AM, Zhang XY, Ke ZP. Apigenin sensitizes BEL-7402/ADM cells to doxorubicin through inhibiting miR-101/Nrf2 pathway. Oncotarget. 2017;8:82085–91.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Fan P, Zhang Y, Liu L, Zhao Z, Yin Y, Xiao X, et al. Continuous exposure of pancreatic cancer cells to dietary bioactive agents does not induce drug resistance unlike chemotherapy. Cell Death Dis. 2016;7:e3346.

    Article  Google Scholar 

  117. Hwang ES, Jeffery EH. Induction of quinone reductase by sulforaphane and sulforaphane N-acetylcysteine conjugate in murine hepatoma cells. J Med Food. 2005;8:198–203.

    Article  CAS  PubMed  Google Scholar 

  118. Volonte D, Liu Z, Musille PM, Stoppani E, Wakabayashi N, Di YP, et al. Inhibition of nuclear factor-erythroid 2-related factor (Nrf2) by caveolin-1 promotes stress-induced premature senescence. Mol Biol Cell. 2013;24:1852–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Su X, Jiang X, Meng L, Dong X, Shen Y, Xin Y. Anticancer activity of sulforaphane: The epigenetic mechanisms and the Nrf2 signaling pathway. Oxid Med Cell Longev. 2018;2018:5438179.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Shannon J, Ho E, Naik A, Troxell M, Cox A, Maxcy C, et al. Sulforaphane supplementation in women newly diagnosed with DCIS: a biomarker study. J Clin Oncol. 2010;28:TPS143.

    Article  Google Scholar 

  121. Myzak MC, Karplus PA, Chung FL, Dashwood RH. A novel mechanism of chemoprotection by sulforaphane: Inhibition of histone deacetylase. Cancer Res. 2004;64:5767–74.

    Article  CAS  PubMed  Google Scholar 

  122. Galiniak S, Biesiadecki M, Czubat B, Bartusik-Aebisher D. Anti-glycation activity of curcumin. Postep Hig Med Dosw. 2019;73:182–8.

    Article  Google Scholar 

  123. Zammataro M, Sortino MA, Parenti C, Gereau RW, Chiechio S. HDAC and HAT inhibitors differently affect analgesia mediated by group II metabotropic glutamate receptors. Mol Pain. 2014;10:68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Balasubramanyam K, Varier RA, Altaf M, Swaminathan V, Siddappa NB, Ranga U, et al. Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem. 2004;279:51163–71.

    Article  CAS  PubMed  Google Scholar 

  125. Kang J, Chen J, Shi Y, Jia J, Zhang Y. Curcumin-induced histone hypoacetylation: the role of reactive oxygen species. Biochem Pharmacol. 2005;69:1205–13.

    Article  CAS  PubMed  Google Scholar 

  126. Yang J, Cao Y, Sun J, Zhang Y. Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells. Med Oncol. 2010;27:1114–8.

    Article  CAS  PubMed  Google Scholar 

  127. Barve A, Khor TO, Hao X, Keum YS, Yang CS, Reddy B, et al. Murine prostate cancer inhibition by dietary phytochemicals - curcumin and phenyethylisothiocyanate. Pharm Res. 2008;25:2181–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Yallapu MM, Maher DM, Sundram V, Bell MC, Jaggi M, Chauhan SC. Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth. J Ovarian Res. 2010;3:11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Wahl H, Tan L, Griffith K, Choi M, Liu JR. Curcumin enhances Apo2L/TRAIL-induced apoptosis in chemoresistant ovarian cancer cells. Gynecol Oncol. 2007;105:104–12.

    Article  CAS  PubMed  Google Scholar 

  130. Camacho-Barquero L, Villegas I, Sánchez-Calvo JM, Talero E, Sánchez-Fidalgo S, Motilva V, et al. Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. Int Immunopharmacol. 2007;7:333–42.

    Article  CAS  PubMed  Google Scholar 

  131. Moon YJ, Wang X, Morris ME. Dietary flavonoids: Effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro. 2006;20:187–210.

    Article  CAS  PubMed  Google Scholar 

  132. Grill AE, Shahani K, Koniar B, Panyam J. Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic mouse model of HER-2-positive breast cancer. Drug Deliv Transl Res. 2018;8:329–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Feitelson MA, Arzumanyan A, Kulathinal RJ, Blain SW, Holcombe RF, Mahajna J, et al. Sustained proliferation in cancer: Mechanisms and novel therapeutic targets. Semin Cancer Biol. 2015;35:S25–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Liu D, Chen Z. The effect of curcumin on breast cancer cells. J Breast Cancer. 2013;16:133–7.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Mukhopadhyay A, Bueso-Ramos C, Chatterjee D, Pantazis P, Aggarwal BB. Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene. 2001;20:7597–609.

    Article  CAS  PubMed  Google Scholar 

  136. Savouret JF, Quesne M. Resveratrol and cancer: a review. Biomed Pharmacother. 2002;56:84–7.

    Article  CAS  PubMed  Google Scholar 

  137. Srivastava RK, Unterman TG, Shankar S. FOXO transcription factors and VEGF neutralizing antibody enhance antiangiogenic effects of resveratrol. Mol Cell Biochem. 2010;337:201–12.

    Article  CAS  PubMed  Google Scholar 

  138. Jung KH, Lee JH, Quach CHT, Paik JY, Oh H, Park JW, et al. Resveratrol suppresses cancer cell glucose uptake by targeting reactive oxygen species-mediated hypoxia-inducible factor-1α activation. J Nucl Med. 2013;54:2161–7.

    Article  CAS  PubMed  Google Scholar 

  139. He H, Yu FX, Sun C, Luo Y. CBP/p300 and SIRT1 are involved in transcriptional regulation of S-Phase specific histone genes. PLoS One. 2011;6:e22088.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Tili E, Michaille JJ, Alder H, Volinia S, Delmas D, Latruffe N, et al. Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFβ signaling pathway in SW480 cells. Biochem Pharmacol. Biochem Pharmacol. 2010;80:2057–65.

    Article  CAS  PubMed  Google Scholar 

  141. Fukui M, Yamabe N, Zhu BT. Resveratrol attenuates the anticancer efficacy of paclitaxel in human breast cancer cells in vitro and in vivo. Eur J Cancer. 2010;46:1882–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Wang KK, Sampliner RE. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett’s esophagus. Am J Gastroenterol. 2008;103:788–97.

    Article  PubMed  Google Scholar 

  143. Kresty LA, Frankel WL, Hammond CD, Baird ME, Mele JM, Stoner GD, et al. Transitioning from preclinical to clinical chemopreventive assessments of lyophilized black raspberries: interim results show berries modulate markers of oxidative stress in Barrett’s esophagus patients. Nutr Cancer. 2006;54:148–56.

    Article  CAS  PubMed  Google Scholar 

  144. Wang RH, Zheng Y, Kim HS, Xu X, Cao L, Luhasen T, et al. Interplay among BRCA1, SIRT1, and survivin during BRCA1-associated tumorigenesis. Mol Cell. 2008;32:11–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Liu Y, Wu YM, Yu Y, Cao CS, Zhang JH, Li K, et al. Curcumin and resveratrol in combination modulate drug-metabolizing enzymes as well as antioxidant indices during lung carcinogenesis in mice. Hum Exp Toxicol. 2015;34:620–7.

    Article  PubMed  CAS  Google Scholar 

  146. Ziaei S, Halaby R. Dietary isoflavones and breast cancer risk. Medicines. 2017;4:18.

    Article  PubMed Central  CAS  Google Scholar 

  147. Nadal-Serrano M, Pons DG, Sastre-Serra J, Blanquer-Rossellò MM, Roca P, Oliver J. Genistein modulates oxidative stress in breast cancer cell lines according to ERa/ERβ ratio: effects on mitochondrial functionality, sirtuins, uncoupling protein 2 and antioxidant enzymes. Int J Biochem Cell Biol. 2013;45:2045–51.

    Article  CAS  PubMed  Google Scholar 

  148. Zhou Y, Liu X. The role of estrogen receptor beta in breast cancer. Biomark Res. 2020;8:39.

    Article  PubMed  PubMed Central  Google Scholar 

  149. Fang MZ, Chen D, Sun Y, Jin Z, Christman JK, Yang CS. Reversal of hypermethylation and reactivation of p16INK4a, RARβ, and MGMT genes by genistein and other isoflavones from soy. Clin Cancer Res. 2005;11:7033–41.

    Article  CAS  PubMed  Google Scholar 

  150. Pudenz M, Roth K, Gerhauser C. Impact of soy isoflavones on the epigenome in cancer prevention. Nutrients. 2014;6:4218–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  151. Bosutti A, Zanconati F, Grassi G, Dapas B, Passamonti S, Scaggiante B. Epigenetic and miRNAs dysregulation in prostate cancer: the role of nutraceuticals. Anticancer Agents Med Chem. 2016;16:1385–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Chang WW, Hu FW, Yu CC, Wang HH, Feng HP, Lan C, et al. Quercetin in elimination of tumor initiating stem-like and mesenchymal transformation property in head and neck cancer. Head Neck. 2013;35:413–9.

    Article  PubMed  Google Scholar 

  153. Cao C, Sun L, Mo W, Sun L, Luo J, Yang Z, et al. Quercetin mediates β-catenin in pancreatic cancer stem-like cells. Pancreas. 2015;44:1334–9.

    Article  CAS  PubMed  Google Scholar 

  154. Nosrati N, Bakovic M, Paliyath G. Molecular mechanisms and pathways as targets for cancer prevention and progression with dietary compounds. Int J Mol Sci. 2017;18:2050.

    Article  PubMed Central  CAS  Google Scholar 

  155. Huang YT, Hwang JJ, Lee PP, Ke FC, Huang JH, Huang CJ, et al. Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor. Br J Pharmacol. 1999;128:999–1010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Ou HC, Lee WJ, Da Lee S, Huang CY, Chiu TH, Tsai KL, et al. Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway. Toxicol Appl Pharmacol. 2010;248:134–43.

    Article  CAS  PubMed  Google Scholar 

  157. Shamshoum H, Vlavcheski F, Tsiani E. Anticancer effects of oleuropein. BioFactors. 2017;43:517–28.

    Article  CAS  PubMed  Google Scholar 

  158. Han J, Talorete TPN, Yamada P, Isoda H. Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells. Cytotechnology. 2009;59:45–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Simsek EN, Uysal T. In vitro investigation of cytotoxic and apoptotic effects of Cynara L. species in colorectal cancer cells. Asian Pacific J Cancer Prev. 2013;14:6791–5.

    Article  Google Scholar 

  160. Miccadei S, Di Venere D, Cardinali A, Romano F, Durazzo A, Foddai MS, et al. Antioxidative and apoptotic properties of polyphenolic extracts from edible part of artichoke (Cynara scolymus L.) on cultured rat hepatocytes and on human hepatoma cells. Nutr Cancer. 2008;60:276–83.

    Article  CAS  PubMed  Google Scholar 

  161. Mileo AM, Di Venere D, Abbruzzese C, Miccadei S. Long term exposure to polyphenols of artichoke (cynara scolymus L.) Exerts induction of senescence driven growth arrest in the MDA-MB231 human breast cancer cell line. Oxid Med Cell Longev. 2015;2015:363827.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Al-Radadi NS. Artichoke (Cynara scolymus L.,) mediated rapid analysis of silver nanoparticles and their utilisation on the cancer cell treatments. J Comput Theor Nanosci. 2018;15:1818–29.

    Article  CAS  Google Scholar 

  163. Cairney CJ, Bilsland AE, Evans TRJ, Roffey J, Bennett DC, Narita M, et al. Cancer cell senescence: a new frontier in drug development. Drug Discov Today. 2012;17:269–76.

    Article  CAS  PubMed  Google Scholar 

  164. Ewald JA, Desotelle JA, Wilding G, Jarrard DF. Therapy-induced senescence in cancer. J Natl Cancer Inst. 2010;102:1536–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Naylor RM, Baker DJ, Van Deursen JM. Senescent cells: a novel therapeutic target for aging and age-related diseases. Clin Pharmacol Ther. 2013;93:105–16.

    Article  CAS  PubMed  Google Scholar 

  166. Childs BG, Gluscevic M, Baker DJ, Laberge RM, Marquess D, Dananberg J, et al. Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov. 2017;16:718–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Guo X, Ngo B, Modrek A, Lee W-H. Targeting tumor suppressor networks for cancer therapeutics. Curr Drug Targets. 2014;15:2–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Lai D, Visser-Grieve S, Yang X. Tumour suppressor genes in chemotherapeutic drug response. Biosci Rep. 2012;32:361–74.

    Article  CAS  PubMed  Google Scholar 

  169. Qian Y, Chen X. Senescence regulation by the p53 protein family. Methods Mol Biol. 2013;965:37–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Larsson LG. Oncogene- and tumor suppressor gene-mediated suppression of cellular senescence. Semin Cancer Biol. 2011;21:367–76.

    Article  CAS  PubMed  Google Scholar 

  171. Lan L, Holland JD, Qi J, Grosskopf S, Rademann J, Vogel R, et al. Shp2 signaling suppresses senescence in Py MT -induced mammary gland cancer in mice. EMBO J. 2015;34:2383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Law ME, Corsino PE, Narayan S, Law BK. Cyclin-dependent kinase inhibitors as anticancer therapeutics. Mol Pharmacol. 2015;88:846–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Al Bitar S, Gali-Muhtasib H. The role of the cyclin dependent kinase inhibitor p21cip1/waf1 in targeting cancer: molecular mechanisms and novel therapeutics. Cancers (Basel). 2019;11:1475.

    Article  CAS  Google Scholar 

  174. Haferkamp S, Becker TM, Scurr LL, Kefford RF, Rizos H. p16INK4a-induced senescence is disabled by melanoma-associated mutations. Aging Cell. 2008;7:733–45.

    Article  CAS  PubMed  Google Scholar 

  175. Mijit M, Caracciolo V, Melillo A, Amicarelli F, Giordano A. Role of p53 in the regulation of cellular senescence. Biomolecules. 2020;10:420.

    Article  CAS  PubMed Central  Google Scholar 

  176. Herbig U, Jobling WA, Chen BPC, Chen DJ, Sedivy JM. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21CIP1, but not p16INK4a. Mol Cell. 2004;14:501–13.

    Article  CAS  PubMed  Google Scholar 

  177. Kim R, Osaki A, Tanabe K, Toge T. Neoadjuvant chemotherapy for local advanced breast cancer with stage IIIB. Oncol Rep. 2004;11:1265–72.

    CAS  PubMed  Google Scholar 

  178. Yeo EJ, Hwang YC, Kang CM, Kim IH, Kim DI, Parka JS, et al. Senescence-like changes induced by hydroxyurea in human diploid fibroblasts. Exp Gerontol. 2000;35:553–71.

    Article  CAS  PubMed  Google Scholar 

  179. Chang BD, Xuan Y, Broude EV, Zhu H, Schott B, Fang J, et al. Role of p53 and p21(waf1/cip1) in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs. Oncogene. 1999;18:4808–18.

    Article  CAS  PubMed  Google Scholar 

  180. Zhang Y, Yang JM. The impact of cellular senescence in cancer therapy: is it true or not? Acta Pharmacol Sin. 2011;32:1199–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Sin S, Kim SY, Kim SS. Chronic treatment with ginsenoside Rg3 induces Akt-dependent senescence in human glioma cells. Int J Oncol. 2012;41:1669–74.

    Article  CAS  PubMed  Google Scholar 

  182. Li YB, Gao JL, Zhong ZF, Hoi PM, Lee SMY, Wang YT. Bisdemethoxycurcumin suppresses MCF-7 cells proliferation by inducing ROS accumulation and modulating senescence-related pathways. Pharmacol Rep. 2013;65:700–9.

    Article  CAS  PubMed  Google Scholar 

  183. Roy N, Elangovan I, Kopanja D, Bagchi S, Raychaudhuri P. Tumor regression by phenethyl isothiocyanate involves DDB2. Cancer Biol Ther. 2013;14:108–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Mileo AM, Di Venere D, Linsalata V, Fraioli R, Miccadei S. Artichoke polyphenols induce apoptosis and decrease the invasive potential of the human breast cancer cell line MDA-MB231. J Cell Physiol. 2012;227:3301–9.

    Article  CAS  PubMed  Google Scholar 

  185. Salekzamani S, Ebrahimi-Mameghani M, Rezazadeh K. The antioxidant activity of artichoke (Cynara scolymus): a systematic review and meta-analysis of animal studies. Phyther Res. 2019;33:55–71.

    Article  CAS  Google Scholar 

  186. Luo H, Yang A, Schulte BA, Wargovich MJ, Wang GY. Resveratrol induces premature senescence in lung cancer cells via ROS-mediated DNA damage. PLoS One. 2013;8:e60065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Yang Q, Wang B, Zang W, Wang X, Liu Z, Li W, et al. Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and senescence in a Sirt1-dependent manner. PLoS One. 2013;8:e70627.

    Article  PubMed  PubMed Central  Google Scholar 

  188. Zamin LL, Filippi-Chiela EC, Dillenburg-Pilla P, Horn F, Salbego C, Lenz G. Resveratrol and quercetin cooperate to induce senescence-like growth arrest in C6 rat glioma cells. Cancer Sci. 2009;100:1655–62.

    Article  CAS  PubMed  Google Scholar 

  189. Cho RW, Clarke MF. Recent advances in cancer stem cells. Curr Opin Genet Dev. 2008;18:48–53.

    Article  CAS  PubMed  Google Scholar 

  190. Ye J, Wu D, Wu P, Chen Z, Huang J. The cancer stem cell niche: cross talk between cancer stem cells and their microenvironment. Tumor Biol. 2014;35:3945–51.

    Article  CAS  Google Scholar 

  191. Maccalli C, De Maria R. Cancer stem cells: perspectives for therapeutic targeting. Cancer Immunol Immunother. 2015;64:91–7.

    Article  PubMed  Google Scholar 

  192. Cojoc M, Mäbert K, Muders MH, Dubrovska A. A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms. Semin Cancer Biol. 2015;31:16–27.

    Article  CAS  PubMed  Google Scholar 

  193. Yang L, Shi P, Zhao G, Xu J, Peng W, Zhang J, et al. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther. 2020;5:8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  194. Chen K, Huang YH, Chen JL. Understanding and targeting cancer stem cells: therapeutic implications and challenges. Acta Pharmacol Sin. 2013;34:732–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Takebe N, Harris PJ, Warren RQ, Ivy SP. Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol. 2011;8:97–106.

    Article  CAS  PubMed  Google Scholar 

  196. Song IS. Mitochondria as therapeutic targets for cancer stem cells. World J Stem Cells. 2015;7:418.

    Article  PubMed  PubMed Central  Google Scholar 

  197. Ramos EK, Hoffmann AD, Gerson SL, Liu H. New opportunities and challenges to defeat cancer stem cells. Trends Cancer. 2017;3:780–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Hill RP, Marie-Egyptienne DT, Hedley DW. Cancer stem cells, hypoxia and metastasis. Semin Radiat Oncol. 2009;19:106–11.

    Article  PubMed  Google Scholar 

  199. Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov. 2011;10:767–77.

    Article  CAS  PubMed  Google Scholar 

  200. Landskron G, De La Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res. 2014;2014:149185.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  201. Zhang G, Yang P, Guo P, Miele L, Sarkar FH, Wang Z, et al. Unraveling the mystery of cancer metabolism in the genesis of tumor-initiating cells and development of cancer. Biochim Biophys Acta. 1836;2013:49–59.

    Google Scholar 

  202. Takebe N, Miele L, Harris PJ, Jeong W, Bando H, Kahn M, et al. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol. 2015;12:445–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Bao Y, Wang W, Zhou Z, Sun C. Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention. PLoS One. 2014;9:e114764.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  204. Zhang Y. Cancer-preventive isothiocyanates: measurement of human exposure and mechanism of action. Mutat Res. 2004;555:173–90.

    Article  CAS  PubMed  Google Scholar 

  205. Naujokat C, McKee DL. The “Big Five” phytochemicals targeting cancer stem cells: curcumin, EGCG, sulforaphane, resveratrol and genistein. Curr Med Chem. 2020;27:1.

    Google Scholar 

  206. Bayat Mokhtari R, Baluch N, Homayouni TS, Morgatskaya E, Kumar S, Kazemi P, et al. The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review. J Cell Commun Signal. 2018;12:91–101.

    Article  PubMed  Google Scholar 

  207. Li Y, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, et al. Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res. 2010;16:2580–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Rodova M, Fu J, Watkins DN, Srivastava RK, Shankar S. Sonic Hedgehog signaling inhibition provides opportunities for targeted therapy by sulforaphane in regulating pancreatic cancer stem cell self-renewal. PLoS One. 2012;7:e46083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Thyagarajan A, Forino AS, Konger RL, Sahu RP. Dietary polyphenols in cancer chemoprevention: implications in pancreatic cancer. Antioxidants. 2020;9:1–20.

    Article  CAS  Google Scholar 

  210. Zhou W, Kallifatidis G, Baumann B, Rausch V, Mattern J, Gladkich J, et al. Dietary polyphenol quercetin targets pancreatic cancer stem cells. Int J Oncol. 2010;37:551–61.

    CAS  PubMed  Google Scholar 

  211. Brito A, Ribeiro M, Abrantes A, Pires A, Teixo R, Tralhao J, et al. Quercetin in cancer treatment, alone or in combination with conventional therapeutics? Curr Med Chem. 2015;22:3025–39.

    Article  CAS  PubMed  Google Scholar 

  212. He FJ, Chen JQ. Consumption of soybean, soy foods, soy isoflavones and breast cancer incidence: differences between Chinese women and women in Western countries and possible mechanisms. Food Sci Hum Wellness. 2013;2:146–61.

    Article  Google Scholar 

  213. Messina M. Soy and health update: evaluation of the clinical and epidemiologic literature. Nutrients. 2016;8:754.

    Article  PubMed Central  Google Scholar 

  214. Montales MTE, Rahal OM, Nakatani H, Matsuda T, Simmen RCM. Repression of mammary adipogenesis by genistein limits mammosphere formation of human MCF-7 cells. J Endocrinol. 2013;218:135–49.

    Article  CAS  PubMed  Google Scholar 

  215. Subramaniam D, Kaushik G, Dandawate P, Anant S. Targeting cancer stem cells for chemoprevention of pancreatic cancer. Curr Med Chem. 2017;25:2585–94.

    Article  CAS  Google Scholar 

  216. Wang Y, Bu C, Wu K, Wang R, Wang J. Curcumin protects the pancreas from acute pancreatitis via the mitogen-activated protein kinase signaling pathway. Mol Med Rep. 2019;20:3027–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  217. Howells LM, Moiseeva EP, Neal CP, Foreman BE, Andreadi CK, Sun YY, et al. Predicting the physiological relevance of in vitro cancer preventive activities of phytochemicals. Acta Pharmacol Sin. 2007;28:1274–304.

    Article  CAS  PubMed  Google Scholar 

  218. Siddappa G, Kulsum S, Ravindra DR, Kumar VV, Raju N, Raghavan N, et al. Curcumin and metformin-mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells. Mol Carcinog. 2017;56:2446–60.

    Article  CAS  PubMed  Google Scholar 

  219. Sancho P, Barneda D, Heeschen C. Hallmarks of cancer stem cell metabolism. Br J Cancer. 2016;114:1305–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Viale A, Corti D, Draetta GF. Tumors and mitochondrial respiration: a neglected connection. Cancer Res. 2015;75:3685–6.

    Article  PubMed  CAS  Google Scholar 

  221. De Francesco EM, Sotgia F, Lisanti MP. Cancer stem cells (CSCs): metabolic strategies for their identification and eradication. Biochem J. 2018;475:1611–34.

    Article  PubMed  CAS  Google Scholar 

  222. Boros LG, Bassilian S, Lim S, Lee WNP. Genistein inhibits nonoxidative ribose synthesis in MIA pancreatic adenocarcinoma cells: a new mechanism of controlling tumor growth. Pancreas. 2001;22:1–7.

    Article  CAS  PubMed  Google Scholar 

  223. Zhao H, Orhan YC, Zha X, Esencan E, Chatterton RT, Bulun SE. AMP-activated protein kinase and energy balance in breast cancer. Am J Transl Res. 2017;9:197–213.

    CAS  PubMed  PubMed Central  Google Scholar 

  224. Manu KA, Cao PHA, Chai TF, Casey PJ, Wang M. P21Cip1/Waf1 coordinate autophagy, proliferation and apoptosis in response to metabolic stress. Cancers (Basel). 2019;11:1112.

    Article  CAS  Google Scholar 

  225. Fabiani R, Vella N, Rosignoli P. Epigenetic modifications induced by olive oil and its phenolic compounds: a systematic review. Molecules. 2021;26:273.

    Article  CAS  PubMed Central  Google Scholar 

  226. Tanveer S, Fathi E, Guy F. Towards new anticancer strategies by targeting cancer stem cells with phytochemical compounds. In: Shostak S, editor. Cancer stem cells – the cutting edge. London: IntechOpen; 2011. p. 431–56.

    Google Scholar 

  227. Lee W-H, Loo C-Y, Bebawy M, Luk F, Mason R, Rohanizadeh R. Curcumin and its derivatives: their application in neuropharmacology and neuroscience in the 21st century. Curr Neuropharmacol. 2013;11:338–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Yang CL, Ma YG, Xue YX, Liu YY, Xie H, Qiu GR. Curcumin induces small cell lung cancer NCI-H446 cell apoptosis via the reactive oxygen species-mediated mitochondrial pathway and not the cell death receptor pathway. DNA Cell Biol. 2012;31:139–50.

    Article  CAS  PubMed  Google Scholar 

  229. Shin HJ, Han JM, Choi YS, Jung HJ. Pterostilbene suppresses both cancer cells and cancer stem-like cells in cervical cancer with superior bioavailability to resveratrol. Molecules. 2020;25:228.

    Article  CAS  PubMed Central  Google Scholar 

  230. McCormack D, McFadden D. A review of pterostilbene antioxidant activity and disease modification. Oxid Med Cell Longev. 2013;2013:575482.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  231. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009;2:270–8.

    Article  PubMed  PubMed Central  Google Scholar 

  233. Prasad S, Phromnoi K, Yadav VR, Chaturvedi MM, Aggarwal BB. Targeting inflammatory pathways by flavonoids for prevention and treatment of cancer. Planta Med. 2010;76:1044–63.

    Article  CAS  PubMed  Google Scholar 

  234. Koklesova L, Liskova A, Samec M, Buhrmann C, Samuel SM, Varghese E, et al. Carotenoids in cancer apoptosis—the road from bench to bedside and back. Cancers (Basel). 2020;12:2425.

    Article  CAS  Google Scholar 

  235. Soundararajan P, Kim JS. Anti-carcinogenic glucosinolates in cruciferous vegetables and their antagonistic effects on prevention of cancers. Molecules. 2018;23:2983.

    Article  PubMed Central  CAS  Google Scholar 

  236. Yadav UP, Singh T, Kumar P, Sharma P, Kaur H, Sharma S, et al. Metabolic adaptations in cancer stem cells. Front Oncol. 2020;10:1010.

    Article  PubMed  PubMed Central  Google Scholar 

  237. Robey IF, Baggett BK, Kirkpatrick ND, Roe DJ, Dosescu J, Sloane BF, et al. Bicarbonate increases tumor pH and inhibits spontaneous metastases. Cancer Res. 2009;69:2260–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Shamim U, Hanif S, Albanyan A, Beck FWJ, Bao B, Wang Z, et al. Resveratrol-induced apoptosis is enhanced in low pH environments associated with cancer. J Cell Physiol. 2012;227:1493–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Sharma A, Kaur M, Katnoria JK, Nagpal AK. Polyphenols in food: cancer prevention and apoptosis induction. Curr Med Chem. 2017;25:4740–57.

    Article  CAS  Google Scholar 

  240. Yan Y, Liu N, Hou N, Dong L, Li J. Chlorogenic acid inhibits hepatocellular carcinoma in vitro and in vivo. J Nutr Biochem. 2017;46:68–73.

    Article  CAS  PubMed  Google Scholar 

  241. Bin Hafeez B, Asim M, Siddiqui IA, Adhami VM, Murtaza I, Delphinidin MH. a dietary anthocyanidin in pigmented fruits and vegetables: a new weapon to blunt prostate cancer growth. Cell Cycle. 2008;7:3320–6.

    Article  CAS  PubMed  Google Scholar 

  242. Liu W, Xu J, Wu S, Liu Y, Yu X, Chen J, et al. Selective anti-proliferation of HER2-positive breast cancer cells by anthocyanins identified by high-throughput screening. PLoS One. 2013;8:e81586.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  243. Tsang WP, Kwok TT. Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells. J Nutr Biochem. 2010;21:140–6.

    Article  CAS  PubMed  Google Scholar 

  244. Bhardwaj V, Mandal AKA. Next-generation sequencing reveals the role of epigallocatechin-3-gallate in regulating putative novel and known microRNAs which target the MAPK pathway in non-small-cell lung cancer A549 cells. Molecules. 2019;24:368.

    Article  PubMed Central  CAS  Google Scholar 

  245. Borutinskaitė V, Virkšaitė A, Gudelytė G, Navakauskienė R. Green tea polyphenol EGCG causes anti-cancerous epigenetic modulations in acute promyelocytic leukemia cells. Leuk Lymphoma. 2018;59:469–78.

    Article  PubMed  CAS  Google Scholar 

  246. Xie J, Yun JP, Yang YN, Hua F, Zhang XW, Lin H, et al. A novel ECG analog 4-(S)-(2,4,6-trimethylthiobenzyl)-epigallocatechin gallate selectively induces apoptosis of B16-F10 melanoma via activation of autophagy and ROS. Sci Rep. 2017;7:42194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. Russo M, Spagnuolo C, Tedesco I, Bilotto S, Russo GL. The flavonoid quercetin in disease prevention and therapy: facts and fancies. Biochem Pharmacol. 2012;83:6–15.

    Article  CAS  PubMed  Google Scholar 

  248. Wu Q, Needs PW, Lu Y, Kroon PA, Ren D, Yang X. Different antitumor effects of quercetin, quercetin-3′-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food Funct. 2018;9:1736–46.

    Article  CAS  PubMed  Google Scholar 

  249. Ward AB, Mir H, Kapur N, Gales DN, Carriere PP, Singh S. Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways. World J Surg Oncol. 2018;16:108.

    Article  PubMed  PubMed Central  Google Scholar 

  250. Sambantham S, Radha M, Paramasivam A, Anandan B, Malathi R, Chandra SR, et al. Molecular mechanism underlying hesperetin-induced apoptosis by in silico analysis and in prostate cancer PC-3 cells. Asian Pac J Cancer Prev. 2013;14:4347–52.

    Article  PubMed  Google Scholar 

  251. Zhang J, Wu D, Vikash SJ, Wang J, Yi J, et al. Hesperetin induces the apoptosis of gastric cancer cells via activating mitochondrial pathway by increasing reactive oxygen species. Dig Dis Sci. 2015;60:2985–95.

    Article  CAS  PubMed  Google Scholar 

  252. Palit S, Kar S, Sharma G, Das PK. Hesperetin induces apoptosis in breast carcinoma by triggering accumulation of ROS and activation of ASK1/JNK pathway. J Cell Physiol. 2015;230:1729–39.

    Article  CAS  PubMed  Google Scholar 

  253. Lim W, Park S, Bazer FW, Song G. Naringenin-induced apoptotic cell death in prostate cancer cells is mediated via the PI3K/AKT and MAPK signaling pathways. J Cell Biochem. 2017;118:1118–31.

    Article  CAS  PubMed  Google Scholar 

  254. Park S, Lim W, Bazer FW, Song G. Naringenin suppresses growth of human placental choriocarcinoma via reactive oxygen species-mediated P38 and JNK MAPK pathways. Phytomedicine. 2018;50:238–46.

    Article  CAS  PubMed  Google Scholar 

  255. Park HJ, Choi YJ, Lee JH, Nam MJ. Naringenin causes ASK1-induced apoptosis via reactive oxygen species in human pancreatic cancer cells. Food Chem Toxicol. 2017;99:1–8.

    Article  CAS  PubMed  Google Scholar 

  256. Pandey M, Kaur P, Shukla S, Abbas A, Fu P, Gupta S. Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: In vitro and in vivo study. Mol Carcinog. 2012;51:952–62.

    Article  CAS  PubMed  Google Scholar 

  257. Dei Cas M, Ghidoni R. Cancer prevention and therapy with polyphenols: sphingolipid-mediated mechanisms. Nutrients. 2018;10:940.

    Article  PubMed Central  CAS  Google Scholar 

  258. Tian T, Li J, Li B, Wang Y, Li M, Ma D, et al. Genistein exhibits anti-cancer effects via down-regulating FoxM1 in H446 small-cell lung cancer cells. Tumor Biol. 2014;35:4137–45.

    Article  CAS  Google Scholar 

  259. Majid S, Dar AA, Ahmad AE, Hirata H, Kawakami K, Shahryari V, et al. BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer. Carcinogenesis. 2009;30:662–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  260. Luo H, Wang L, Schulte BA, Yang A, Tang S, Wang GY. Resveratrol enhances ionizing radiation-induced premature senescence in lung cancer cells. Int J Oncol. 2013;43:1999–2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  261. Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-κB-regulated gene products. Cancer Res. 2007;67:3853–61.

    Article  CAS  PubMed  Google Scholar 

  262. Alexandrow MG, Song LJ, Altiok S, Gray J, Haura EB, Kumar NB. Curcumin: a novel Stat3 pathway inhibitor for chemoprevention of lung cancer. Eur J Cancer Prev. 2012;21:407–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  263. Yang CW, Chang CL, Lee HC, Chi CW, Pan JP, Yang WC. Curcumin induces the apoptosis of human monocytic leukemia THP-1 cells via the activation of JNK/ERK Pathways. BMC Complem Altern Med. 2012;12:22.

    Article  CAS  Google Scholar 

  264. Stocco B, Toledo KA, Fumagalli HF, Bianchini FJ, Fortes VS, Fonseca MJV, et al. Biotransformed soybean extract induces cell death of estrogen-dependent breast cancer cells by modulation of apoptotic proteins. Nutr Cancer. 2015;67:612–9.

    Article  PubMed  Google Scholar 

  265. Park HJ, Jeon YK, You DH, Nam MJ. Daidzein causes cytochrome c-mediated apoptosis via the Bcl-2 family in human hepatic cancer cells. Food Chem Toxicol. 2013;60:542–9.

    Article  CAS  PubMed  Google Scholar 

  266. Wang LG, Beklemisheva A, Liu XM, Ferrari AC, Feng J, Chiao JW. Dual action on promoter demethylation and chromatin by an isothiocyanate restored GSTP1 silenced in prostate cancer. Mol Carcinog. 2007;46:24–31.

    Article  CAS  PubMed  Google Scholar 

  267. Chen PY, Lin KC, Lin JP, Tang NY, Yang JS, Lu KW, et al. Phenethyl isothiocyanate (PEITC) inhibits the growth of human oral squamous carcinoma hsc-3 cells through g(0)/g(1) phase arrest and mitochondria-mediated apoptotic cell death. Evid Based Complem Altern Med. 2012;2012:718320.

    Article  Google Scholar 

  268. Ho CC, Lai KC, Hsu SC, Kuo CL, Ma CY, Lin ML, et al. Benzyl isothiocyanate (BITC) inhibits migration and invasion of human gastric cancer AGS cells via suppressing ERK signal pathways. Hum Exp Toxicol. 2011;30:296–306.

    Article  CAS  PubMed  Google Scholar 

  269. Im E, Yeo C, Lee EO. Luteolin induces caspase-dependent apoptosis via inhibiting the AKT/osteopontin pathway in human hepatocellular carcinoma SK-Hep-1 cells. Life Sci. 2018;209:259–66.

    Article  CAS  PubMed  Google Scholar 

  270. Kang KA, Piao MJ, Ryu YS, Hyun YJ, Park JE, Shilnikova K, et al. Luteolin induces apoptotic cell death via antioxidant activity in human colon cancer cells. Int J Oncol. 2017;51:1169–78.

    Article  CAS  PubMed  Google Scholar 

  271. Zhang Q, Yang J, Wang J. Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer. Oncol Lett. 2016;12:4767–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  272. Mak KK, Wu ATH, Lee WH, Chang TC, Chiou JF, Wang LS, et al. Pterostilbene, a bioactive component of blueberries, suppresses the generation of breast cancer stem cells within tumor microenvironment and metastasis via modulating NF-κB/microRNA 448 circuit. Mol Nutr Food Res. 2013;57:1123–34.

    Article  CAS  PubMed  Google Scholar 

  273. Li Y, Zhang T. Targeting cancer stem cells with sulforaphane, a dietary component from broccoli and broccoli sprouts. Future Oncol. 2013;9:1097–103.

    Article  CAS  PubMed  Google Scholar 

  274. Choudhari AS, Mandave PC, Deshpande M, Ranjekar P, Prakash O. Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Front Pharmacol. 2020;10:1614.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  275. Pastorelli D, Fabricio ASC, Giovanis P, D’Ippolito S, Fiduccia P, Soldà C, et al. Phytosome complex of curcumin as complementary therapy of advanced pancreatic cancer improves safety and efficacy of gemcitabine: Results of a prospective phase II trial. Pharmacol Res. 2018;132:72–9.

    Article  CAS  PubMed  Google Scholar 

  276. Chen J, Song Y, Zhang L. Lycopene/tomato consumption and the risk of prostate cancer: a systematic review and meta-analysis of prospective studies. J Nutr Sci Vitaminol (Tokyo). 2013;59:213–23.

    Article  CAS  PubMed  Google Scholar 

  277. Gontero P, Marra G, Soria F, Oderda M, Zitella A, Baratta F, et al. A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or “chemopromotion”? Prostate. 2015;75:1177–86.

    Article  CAS  PubMed  Google Scholar 

  278. Beynon RA, Richmond RC, Santos Ferreira DL, Ness AR, May M, Smith GD, et al. Investigating the effects of lycopene and green tea on the metabolome of men at risk of prostate cancer: The ProDiet randomised controlled trial. Int J Cancer. 2019;144:1918–28.

    Article  CAS  PubMed  Google Scholar 

  279. Paller CJ, Rudek MA, Zhou XC, Wagner WD, Hudson TS, Anders N, et al. A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: Safety, tolerability, and dose determination. Prostate. 2015;75:1518–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  280. Alumkal JJ, Slottke R, Schwartzman J, Cherala G, Munar M, Graff JN, et al. A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer. Invest New Drugs. 2015;33:480–9.

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. Pankajkumar Yadav and Amita Verma contributed equally to this work.

Authors and Affiliations

  1. Bioorganic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, India

    Ekta Yadav & Amita Verma

  2. Pharmaceutics Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, India

    Pankajkumar Yadav

  3. King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia

    Mohammad A. Kamal

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  1. Ekta Yadav
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  2. Pankajkumar Yadav
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  3. Mohammad A. Kamal
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  4. Amita Verma
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  1. King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia

    Shams Tabrez

  2. Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia

    Mohammad Imran Khan

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Yadav, E., Yadav, P., Kamal, M.A., Verma, A. (2021). Polyphenols as Modulators of Oxidative Stress in Cancer Disease. In: Tabrez, S., Imran Khan, M. (eds) Polyphenols-based Nanotherapeutics for Cancer Management. Springer, Singapore. https://doi.org/10.1007/978-981-16-4935-6_5

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