The mechanisms of wine phenolic compounds for preclinical anticancer therapeutics

  • Jing Duan College of Enology, Northwest A&F University, Yangling, China
  • Hua Guo College of Enology, Northwest A&F University, Yangling, China
  • Yulin Fang College of Enology, Northwest A&F University, Yangling, China
  • Guangbiao Zhou State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Keywords: wine; phenolic compounds; mechanism; chemotherapy


Background: Wine is one of the oldest and most popular drinks worldwide, which is rich in phenolic compounds. Epidemiological studies show that moderate consumption of wine can reduce the risk of certain diseases, and this effect is attributed to its phenolic compounds.

Objective: The objective of this review was to elaborate the effects of wine-derived phenolic compounds for preclinical anticancer therapeutics and their major mechanisms.

Methods: In this review, we discuss the classification and content of common phenolic compounds in wine and summarize previous studies that have evaluated the anticancer properties of wine-derived phenolic compounds and their mechanisms.

Results: Wine-derived phenolic compounds have been proven to participate in several mechanisms against cancers, including deoxyribonucleic acid damage, oxidative stress, cell proliferation, cell cycle arrest, cell apoptosis, autophagy, cell invasion and metastasis, immunity and metabolism, regulation of multiple signaling molecules, and gene expression. However, the exact anticancer mechanisms of the phenolic compounds in wine need to be further investigated.

Conclusion: Wine-derived phenolic compounds are promising chemoprotective and chemotherapeutic agents for cancer.


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  1. Arranz S, Chiva-Blanch G, Valderas-Martinez P, Medina-Remon A, Lamuela-Raventos RM, Estruch R. Wine, beer, alcohol and polyphenols on cardiovascular disease and cancer. Nutrients 2012; 4: 759–81. doi: 10.3390/nu4070759

  2. Stockley C, Teissedre PL, Boban M, Di Lorenzo C, Restani P. Bioavailability of wine-derived phenolic compounds in humans: a review. Food Funct 2012; 3: 995–1007. doi: 10.1039/c2fo10208k

  3. Waterhouse AL. Wine phenolics. Annals of the New York Academy of Sciences 2002; 957: 21–36. doi: 10.1111/j.1749-6632.2002.tb02903.x

  4. Vuorinen H, Maatta K, Torronen R. Content of the flavonols myricetin, quercetin, and kaempferol in Finnish berry wines. J Agric Food Chem 2000; 48: 2675–80. doi: 10.1021/Jf991388o

  5. Ritchey JG, Waterhouse AL. A standard red wine: monomeric phenolic analysis of commercial cabernet sauvignon wines. Am J Enol Viticultre 1999; 50: 91–100. doi: 10.1007/s001220051078

  6. Kovac V, Alonso E, Bourzeix M, Revilla E. Effect of several enological practices on the content of catechins and proanthocyanidins of red wines. J Agric Food Chem 1992; 40: 1953–7. doi: 10.1021/Jf00022a045

  7. Mazza G, Fukumoto L, Delaquis P, Girard B, Ewert B. Anthocyanins, phenolics, and color of Cabernet Franc, Merlot, and Pinot Noir wines from British Columbia. J Agric Food Chem 1999; 47: 4009–17. doi: 10.1021/Jf990449f

  8. Nixdorf SL, Hermosin-Gutierrez I. Brazilian red wines made from the hybrid grape cultivar Isabel: phenolic composition and antioxidant capacity. Anal Chim Acta 2010; 659: 208–15. doi: 10.1016/j.aca.2009.11.058

  9. Pocock KF, Sefton MA, Williams PJ. Taste thresholds of phenolic extracts of French and American Oakwood – the influence of oak phenols on wine flavor. Am J Enol Vitic 1994; 45: 429–34. doi: 10.1016/0924-2244(94)90074-4

  10. Trela BC, Waterhouse AL. Resveratrol: isomeric molar absorptivities and stability. J Agric Food Chem 1996; 44: 1253–7. doi: 10.1021/Jf9504576

  11. Jang MS, Cai EN, Udeani GO, Slowing KV, Thomas CF, Beecher CWW, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997; 275: 218–20. doi: 10.1126/science.275.5297.218

  12. Ruf JC. Overview of epidemiological studies on wine, health and mortality. Drugs Exp Clin Res 2003; 29: 173–9. doi: 10.1358/dot.2003.39.1.740206

  13. German JB, Walzem RL. The health benefits of wine. Annu Rev Nutr 2000; 20: 561–93. doi: 10.1146/annurev.nutr.20.1.561

  14. Apostolidou C, Adamopoulos K, Lymperaki E, Iliadis S, Papapreponis P, Kourtidou-Papadeli C. Cardiovascular risk and benefits from antioxidant dietary intervention with red wine in asymptomatic hypercholesterolemics. Clin Nutr ESPEN 2015; 10: e224–33. doi: 10.1016/j.clnesp.2015.08.001

  15. Robbins KS, Greenspan P, Pegg RB. Effect of pecan phenolics on the release of nitric oxide from murine RAW 264.7 macrophage cells. Food Chem 2016; 212: 681–7. doi: 10.1016/j.foodchem.2016.06.018

  16. Fernandes I, Marques F, de Freitas V, Mateus N. Antioxidant and antiproliferative properties of methylated metabolites of anthocyanins. Food Chem 2013; 141: 2923–33. doi: 10.1016/j.foodchem.2013.05.033

  17. Koosha S, Alshawsh MA, Yeng LC, Seyedan A, Mohamed Z. An association map on the effect of flavonoids on the signaling pathways in colorectal cancer. Int J Med Sci 2016; 13: 374–85. doi: 10.7150/ijms.14485

  18. Fernandes I, Perez-Gregorio R, Soares S, Mateus N, de Freitas V. Wine flavonoids in health and disease prevention. Molecules 2017; 22: 292. doi: 10.3390/Molecules22020292

  19. Mattioli AV, Farinetti A, Gelmini R. Polyphenols, mediterranean diet, and colon cancer. Support Care Cancer 2019; 27: 4035–6. doi: 10.1007/s00520-019-04835-9

  20. Kwon Y. Food-derived polyphenols inhibit the growth of ovarian cancer cells irrespective of their ability to induce antioxidant responses. Heliyon 2018; 4: e00753. doi: 10.1016/j.heliyon.2018.e00753

  21. Braakhuis AJ, Campion P, Bishop KS. Reducing breast cancer recurrence: the role of dietary polyphenolics. Nutrients 2016; 8: 547. doi: 10.3390/nu8090547

  22. Zhou QY, Pan H, Li J. Molecular insights into potential contributions of natural polyphenols to lung cancer treatment. Cancers 2019; 11: 1565. doi: 10.3390/Cancers11101565

  23. Lall RK, Syed DN, Adhami VM, Khan MI, Mukhtar H. Dietary polyphenols in prevention and treatment of prostate cancer. Int J Mol Sci 2015; 16: 3350–76. doi: 10.3390/ijms16023350

  24. Brown L, Kroon PA, Das DK, Das S, Tosaki A, Chan V, et al. The biological responses to resveratrol and other polyphenols from alcoholic beverages. Alcohol Clin Exp Res 2009; 33: 1513–23. doi: 10.1111/j.1530-0277.2009.00989.x

  25. Leifert WR, Abeywardena MY. Grape seed and red wine polyphenol extracts inhibit cellular cholesterol uptake, cell proliferation, and 5-lipoxygenase activity. Nutr Res 2008; 28: 842–50. doi: 10.1016/j.nutres.2008.09.001

  26. Zhang R, Shen L, Miles T, Shen Y, Cordero J, Qi Y, et al. Association of low to moderate alcohol drinking with cognitive functions from middle to older age among US adults. JAMA Netw Open 2020; 3: e207922. doi: 10.1001/jamanetworkopen.2020.7922

  27. Di Castelnuovo A, Costanzo S, Bagnardi V, Donati MB, Iacoviello L, de Gaetano G. Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies. Archiv Intern Med 2006; 166: 2437–45. doi: 10.1001/archinte.166.22.2437

  28. Howard AA, Arnsten JH, Gourevitch MN. Effect of alcohol consumption on diabetes mellitus: a systematic review. Ann Intern Med 2004; 140: 211–9. doi: 10.7326/0003-4819-140-6-200403160-00011

  29. Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ 2011; 342: d671. doi: 10.1136/bmj.d671

  30. Lourida I, Hannon E, Littlejohns TJ, Langa KM, Hypponen E, Kuzma E, et al. Association of lifestyle and genetic risk with incidence of dementia. JAMA 2019; 322: 430–7. doi: 10.1001/jama.2019.9879

  31. De Santis S, Cosa-Linan A, Garcia-Hernandez R, Dmytrenko L, Vargova L, Vorisek I, et al. Chronic alcohol consumption alters extracellular space geometry and transmitter diffusion in the brain. Sci Adv 2020; 6: eaba0154. doi: 10.1126/sciadv.aba0154

  32. Collaborators GBDRF, Forouzanfar MH, Alexander L, Anderson HR, Bachman VF, Biryukov S, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 386: 2287–323. doi: 10.1016/S0140-6736(15)00128-2

  33. Collaborators GBDA. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2018; 392: 1015–35. doi: 10.1016/S0140-6736(18)31310-2

  34. Soleas GJ, Diamandis EP, Goldberg DM. Wine as a biological fluid: history, production, and role in disease prevention. J Clin Lab Anal 1997; 11: 287–313. doi: 10.1002/(Sici)1098-2825(1997)11:5<287::Aid-Jcla6>3.0.Co;2-4

  35. Chang H, Lei L, Zhou Y, Ye F, Zhao G. Dietary flavonoids and the risk of colorectal cancer: an updated meta-analysis of epidemiological studies. Nutrients 2018; 10: 950. doi: 10.3390/nu10070950

  36. George VC, Dellaire G, Rupasinghe HPV. Plant flavonoids in cancer chemoprevention: role in genome stability. J Nutr Biochem 2017; 45: 1–14. doi: 10.1016/j.jnutbio.2016.11.007

  37. Farzaei MH, Singh AK, Kumar R, Croley CR, Pandey AK, Coy-Barrera E, et al. Targeting inflammation by flavonoids: novel therapeutic strategy for metabolic disorders. Int J Mol Sci 2019; 20: 4957. doi: 10.3390/ijms20194957

  38. Price SF, Breen PJ, Valladao M, Watson BT. Cluster sun exposure and quercetin in pinot-noir grapes and wine. Am J Enol Vitic 1995; 46: 187–94.

  39. Awad HM, Boersma MG, Vervoort J, Rietjens IMCM. Peroxidase-catalyzed formation of quercetin quinone methide-glutathione adducts. Archiv Biochem Biophys 2000; 378: 224–33. doi: 10.1006/abbi.2000.1832

  40. Zhang Q, Zhao XH, Wang ZJ. Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis. Toxicol In Vitro 2009; 23: 797–807. doi: 10.1016/j.tiv.2009.04.007

  41. Tan J, Wang B, Zhu L. Regulation of survivin and Bcl-2 in HepG2 cell apoptosis induced by quercetin. Chem Biodivers 2009; 6: 1101–10. doi: 10.1002/cbdv.200800141

  42. Kang ZC, Tsai SJ, Lee H. Quercetin inhibits benzo[a]pyrene-induced DNA adducts in human Hep G2 cells by altering cytochrome P-450 1A1 gene expression. Nutr Cancer 1999; 35: 175–9. doi: 10.1207/S15327914NC352_12

  43. Jeong JH, An JY, Kwon YT, Rhee JG, Lee YJ. Effects of low dose quercetIn: cancer cell-specific inhibition of cell cycle progression. J Cell Biochem 2009; 106: 73–82. doi: 10.1002/jcb.21977

  44. Kuo PC, Liu HF, Chao JI. Survivin and p53 modulate quercetin-induced cell growth inhibition and apoptosis in human lung carcinoma cells. J Biol Chem 2004; 279: 55875–85. doi: 10.1074/jbc.M407985200

  45. Li X, Guo S, Xiong XK, Peng BY, Huang JM, Chen MF, et al. Combination of quercetin and cisplatin enhances apoptosis in OSCC cells by downregulating xIAP through the NF-kappaB pathway. J Cancer 2019; 10: 4509–21. doi: 10.7150/jca.31045

  46. Baker RG, Hayden MS, Ghosh S. NF-kappaB, inflammation, and metabolic disease. Cell Metab 2011; 13: 11–22. doi: 10.1016/j.cmet.2010.12.008

  47. Sun S, Gong F, Liu P, Miao Q. Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway. Gene 2018; 664: 50–7. doi: 10.1016/j.gene.2018.04.045

  48. Shafabakhsh R, Asemi Z. QuercetIn: a natural compound for ovarian cancer treatment. J Ovarian Res 2019; 12: 55. doi: 10.1186/s13048-019-0530-4

  49. Huang RY, Yu YL, Cheng WC, OuYang CN, Fu E, Chu CL. Immunosuppressive effect of quercetin on dendritic cell activation and function. J Immunol 2010; 184: 6815–21. doi: 10.4049/jimmunol.0903991

  50. Nam JS, Sharma AR, Nguyen LT, Chakraborty C, Sharma G, Lee SS. Application of bioactive quercetin in oncotherapy: from nutrition to nanomedicine. Molecules 2016; 21: E108. doi: 10.3390/molecules21010108

  51. Vinayak M, Maurya AK. Quercetin loaded nanoparticles in targeting cancer: recent development. Anticancer Agents Med Chem 2019; 19: 1560–76. doi: 10.2174/1871520619666190705150214

  52. Imran M, Salehi B, Sharifi-Rad J, Aslam Gondal T, Saeed F, Imran A, et al. Kaempferol: a key emphasis to its anticancer potential. Molecules 2019; 24: 2277. doi: 10.3390/molecules24122277

  53. Neuhouser ML. Dietary flavonoids and cancer risk: evidence from human population studies. Nutr Cancer 2004; 50: 1–7. doi: 10.1207/s15327914nc5001_1

  54. Afroze N, Pramodh S, Hussain A, Waleed M, Vakharia K. A review on myricetin as a potential therapeutic candidate for cancer prevention. 3 Biotech 2020; 10: 211. doi: 10.1007/s13205-020-02207-3

  55. Akram M, Iqbal M, Daniyal M, Khan AU. Awareness and current knowledge of breast cancer. Biol Res 2017; 50: 33. doi: 10.1186/s40659-017-0140-9

  56. Li C, Zhao Y, Yang D, Yu Y, Guo H, Zhao Z, et al. Inhibitory effects of kaempferol on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-9. Biochem Cell Biol 2015; 93: 16–27. doi: 10.1139/bcb-2014-0067

  57. Yi X, Zuo J, Tan C, Xian S, Luo C, Chen S, et al. Kaempferol, a flavonoid compound from gynura medica induced apoptosis and growth inhibition in Mcf-7 breast cancer cell. Afr J Tradit Complement Altern Med 2016; 13: 210–5. doi: 10.21010/ajtcam.v13i4.27

  58. Liao W, Chen L, Ma X, Jiao R, Li X, Wang Y. Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells. Eur J Med Chem 2016; 114: 24–32. doi: 10.1016/j.ejmech.2016.02.045

  59. Han X, Liu CF, Gao N, Zhao J, Xu J. Kaempferol suppresses proliferation but increases apoptosis and autophagy by up-regulating microRNA-340 in human lung cancer cells. Biomed Pharmacother 2018; 108: 809–16. doi: 10.1016/j.biopha.2018.09.087

  60. Zhang F, Ma C. Kaempferol suppresses human gastric cancer SNU-216 cell proliferation, promotes cell autophagy, but has no influence on cell apoptosis. Braz J Med Biol Res 2019; 52: e7843. doi: 10.1590/1414-431X20187843

  61. Huang WW, Tsai SC, Peng SF, Lin MW, Chiang JH, Chiu YJ, et al. Kaempferol induces autophagy through AMPK and AKT signaling molecules and causes G2/M arrest via downregulation of CDK1/cyclin B in SK-HEP-1 human hepatic cancer cells. Int J Oncol 2013; 42: 2069–77. doi: 10.3892/ijo.2013.1909

  62. Kim TW, Lee SY, Kim M, Cheon C, Ko SG. Kaempferol induces autophagic cell death via IRE1-JNK-CHOP pathway and inhibition of G9a in gastric cancer cells. Cell Death Dis 2018; 9: 875. doi: 10.1038/s41419-018-0930-1

  63. Ci Y, Zhang Y, Liu Y, Lu S, Cao J, Li H, et al. Myricetin suppresses breast cancer metastasis through down-regulating the activity of matrix metalloproteinase (MMP)-2/9. Phytother Res 2018; 32: 1373–81. doi: 10.1002/ptr.6071

  64. Devi KP, Rajavel T, Habtemariam S, Nabavi SF, Nabavi SM. Molecular mechanisms underlying anticancer effects of myricetin. Life Sci 2015; 142: 19–25. doi: 10.1016/j.lfs.2015.10.004

  65. Ghassemi-Rad J, Maleki M, Knickle AF, Hoskin DW. Myricetin-induced oxidative stress suppresses murine T lymphocyte activation. Cell Biol Int 2018; 42: 1069–75. doi: 10.1002/cbin.10977

  66. Arts IC, van De Putte B, Hollman PC. Catechin contents of foods commonly consumed in The Netherlands. 2. Tea, wine, fruit juices, and chocolate milk. J Agric Food Chem 2000; 48: 1752–7. doi: 10.1021/jf000026+

  67. Al-Dashti YA, Holt RR, Stebbins CL, Keen CL, Hackman RM. Dietary flavanols: a review of select effects on vascular function, blood pressure, and exercise performance. J Am Coll Nutr 2018; 37: 553–67. doi: 10.1080/07315724.2018.1451788

  68. Rogovskii VS, Popov SV, Sturov NV, Shimanovskii NL. The possibility of preventive and therapeutic use of green tea catechins in prostate cancer. Anticancer Agents Med Chem 2019; 19: 1223–31. doi: 10.2174/1871520619666190404153058

  69. Yang CS, Wang H. Cancer preventive activities of tea catechins. Molecules 2016; 21: 1679. doi: 10.3390/molecules21121679

  70. Bimonte S, Cascella M, Leongito M, Palaia R, Caliendo D, Izzo F, et al. An overview of pre-clinical studies on the effects of (-)-epigallocatechin-3-gallate, a catechin found in green tea, in treatment of pancreatic cancer. Recenti Prog Med 2017; 108: 282–7. doi: 10.1701/2715.27715

  71. Shimizu M, Shirakami Y, Sakai H, Adachi S, Hata K, Hirose Y, et al. (-)-Epigallocatechin gallate suppresses azoxymethane-induced colonic premalignant lesions in male C57BL/KsJ-db/db mice. Cancer Prevent Res 2008; 1: 298–304. doi: 10.1158/1940-6207.CAPR-08-0045

  72. Varela-Castillo O, Cordero P, Gutierrez-Iglesias G, Palma I, Rubio-Gayosso I, Meaney E, et al. Characterization of the cytotoxic effects of the combination of cisplatin and flavanol (-)-epicatechin on human lung cancer cell line A549. An isobolographic approach. Exp Oncol 2018; 40: 19–23. doi: 10.31768/2312-8852.2018.40(1):19-23

  73. Lee JS, Kang SU, Hwang HS, Pyun JH, Choung YH, Kim CH. Epicatechin protects the auditory organ by attenuating cisplatin-induced ototoxicity through inhibition of ERK. Toxicol Lett 2010; 199: 308–16. doi: 10.1016/j.toxlet.2010.09.013

  74. Granado-Serrano AB, Martin MA, Haegeman G, Goya L, Bravo L, Ramos S. Epicatechin induces NF-kappaB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) signalling in HepG2 cells. Br J Nutr 2010; 103: 168–79. doi: 10.1017/S0007114509991747

  75. Yamazaki KG, Andreyev AY, Ortiz-Vilchis P, Petrosyan S, Divakaruni AS, Wiley SE, et al. Intravenous (-)-epicatechin reduces myocardial ischemic injury by protecting mitochondrial function. Int J Cardiol 2014; 175: 297–306. doi: 10.1016/j.ijcard.2014.05.009

  76. Godsey J, Grundmann O. Review of various herbal supplements as complementary treatments for oral cancer. J Diet Suppl 2016; 13: 538–50. doi: 10.3109/19390211.2015.1122693

  77. Pae M, Wu D. Immunomodulating effects of epigallocatechin-3-gallate from green tea: mechanisms and applications. Food Funct 2013; 4: 1287–303. doi: 10.1039/c3fo60076a

  78. Gollucke APB, Aguiar O, Barbisan LF, Ribeiro DA. Use of grape polyphenols against carcinogenesis: putative molecular mechanisms of action using in vitro and in vivo test systems. J Med Food 2013; 16: 199–205. doi: 10.1089/jmf.2012.0170

  79. Wang Y, Stevens VL, Shah R, Peterson JJ, Dwyer JT, Gapstur SM, et al. Dietary flavonoid and proanthocyanidin intakes and prostate cancer risk in a prospective cohort of US men. Am J Epidemiol 2014; 179: 974–86. doi: 10.1093/aje/kwu006

  80. King M, Chatelain K, Farris D, Jensen D, Pickup J, Swapp A, et al. Oral squamous cell carcinoma proliferative phenotype is modulated by proanthocyanidins: a potential prevention and treatment alternative for oral cancer. BMC Complement Altern Med 2007; 7: 22. doi: 10.1186/1472-6882-7-22

  81. Engelbrecht AM, Mattheyse M, Ellis B, Loos B, Thomas M, Smith R, et al. Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell line. Cancer Lett 2007; 258: 144–53. doi: 10.1016/j.canlet.2007.08.020

  82. Park SY, Lee YH, Choi KC, Seong AR, Choi HK, Lee OH, et al. Grape seed extract regulates androgen receptor-mediated transcription in prostate cancer cells through potent anti-histone acetyltransferase activity. J Med Food 2011; 14: 9–16. doi: 10.1089/jmf.2010.1264

  83. Smeriglio A, Barreca D, Bellocco E, Trombetta D. Proanthocyanidins and hydrolysable tannins: occurrence, dietary intake and pharmacological effects. Br J Pharmacol 2017; 174: 1244–62. doi: 10.1111/bph.13630

  84. Sieniawska E. Activities of tannins – from in vitro studies to clinical trials. Nat Prod Commun 2015; 10: 1877–84. doi: 10.1177/1934578X1501001118

  85. Kong JM, Chia LS, Goh NK, Chia TF, Brouillard R. Analysis and biological activities of anthocyanins. Phytochemistry 2003; 64: 923–33. doi: 10.1016/s0031-9422(03)00438-2

  86. Jennings A, Welch AA, Fairweather-Tait SJ, Kay C, Minihane AM, Chowienczyk P, et al. Higher anthocyanin intake is associated with lower arterial stiffness and central blood pressure in women. Am J Clin Nutr 2012; 96: 781–8. doi: 10.3945/ajcn.112.042036

  87. Zamora-Ros R, Agudo A, Lujan-Barroso L, Romieu I, Ferrari P, Knaze V, et al. Dietary flavonoid and lignan intake and gastric adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Am J Clin Nutr 2012; 96: 1398–408. doi: 10.3945/ajcn.112.037358

  88. Li D, Wang P, Luo Y, Zhao M, Chen F. Health benefits of anthocyanins and molecular mechanisms: update from recent decade. Crit Rev Food Sci Nutr 2017; 57: 1729–41. doi: 10.1080/10408398.2015.1030064

  89. Lin BW, Gong CC, Song HF, Cui YY. Effects of anthocyanins on the prevention and treatment of cancer. Br J Pharmacol 2017; 174: 1226–43. doi: 10.1111/bph.13627

  90. Liang L, Liu X, He J, Shao Y, Liu J, Wang Z, et al. Cyanidin-3-glucoside induces mesenchymal to epithelial transition via activating Sirt1 expression in triple negative breast cancer cells. Biochimie 2019; 162: 107–15. doi: 10.1016/j.biochi.2019.03.004

  91. Cho E, Chung EY, Jang HY, Hong OY, Chae HS, Jeong YJ, et al. Anti-cancer effect of cyanidin-3-glucoside from mulberry via caspase-3 cleavage and DNA fragmentation in vitro and in vivo. Anticancer Agents Med Chem 2017; 17: 1519–25. doi: 10.2174/1871520617666170327152026

  92. Baster Z, Li L, Kukkurainen S, Chen J, Pentikainen O, Gyorffy B, et al. Cyanidin-3-glucoside binds to talin and modulates colon cancer cell adhesions and 3D growth. FASEB J 2020; 34: 2227–37. doi: 10.1096/fj.201900945R

  93. Liu X, Zhang D, Hao Y, Liu Q, Wu Y, Liu X, et al. Cyanidin curtails renal cell carcinoma tumorigenesis. Cell Physiol Biochem 2018; 46: 2517–31. doi: 10.1159/000489658

  94. Wang H, Li S, Zhang G, Wu H, Chang X. Potential therapeutic effects of cyanidin-3-O-glucoside on rheumatoid arthritis by relieving inhibition of CD38+ NK cells on Treg cell differentiation. Arthritis Res Ther 2019; 21: 220. doi: 10.1186/s13075-019-2001-0

  95. Huang CC, Hung CH, Hung TW, Lin YC, Wang CJ, Kao SH. Dietary delphinidin inhibits human colorectal cancer metastasis associating with upregulation of miR-204-3p and suppression of the integrin/FAK axis. Sci Rep 2019; 9: 18954. doi: 10.1038/s41598-019-55505-z

  96. Lim WC, Kim H, Kim YJ, Park SH, Song JH, Lee KH, et al. Delphinidin inhibits BDNF-induced migration and invasion in SKOV3 ovarian cancer cells. Bioorg Med Chem Lett 2017; 27: 5337–43. doi: 10.1016/j.bmcl.2017.09.024

  97. Lim W, Song G. Inhibitory effects of delphinidin on the proliferation of ovarian cancer cells via PI3K/AKT and ERK 1/2 MAPK signal transduction. Oncol Lett 2017; 14: 810–8. doi: 10.3892/ol.2017.6232

  98. Chen J, Zhou J, Li F, Zhu Y, Zhang W, Yu X. Delphinidin induces autophagy in HER-2+ breast cancer cells via inhibition of AKT/mTOR pathway. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2017; 42: 264–70. doi: 10.11817/j.issn.1672-7347.2017.03.005

  99. Jeong MH, Ko H, Jeon H, Sung GJ, Park SY, Jun WJ, et al. Delphinidin induces apoptosis via cleaved HDAC3-mediated p53 acetylation and oligomerization in prostate cancer cells. Oncotarget 2016; 7: 56767–80. doi: 10.18632/oncotarget.10790

  100. Ho ML, Chen PN, Chu SC, Kuo DY, Kuo WH, Chen JY, et al. Peonidin 3-glucoside inhibits lung cancer metastasis by downregulation of proteinases activities and MAPK pathway. Nutr Cancer 2010; 62: 505–16. doi: 10.1080/01635580903441261

  101. Chen PN, Chu SC, Chiou HL, Chiang CL, Yang SF, Hsieh YS. Cyanidin 3-glucoside and peonidin 3-glucoside inhibit tumor cell growth and induce apoptosis in vitro and suppress tumor growth in vivo. Nutr Cancer 2005; 53: 232–43. doi: 10.1207/s15327914nc5302_12

  102. 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. doi: 10.1371/journal.pone.0081586

  103. Zhang Y, Vareed SK, Nair MG. Human tumor cell growth inhibition by nontoxic anthocyanidins, the pigments in fruits and vegetables. Life Sci 2005; 76: 1465–72. doi: 10.1016/j.lfs.2004.08.025

  104. Wang Y, Lin J, Tian J, Si X, Jiao X, Zhang W, et al. Blueberry malvidin-3-galactoside suppresses hepatocellular carcinoma by regulating apoptosis, proliferation, and metastasis pathways in vivo and in vitro. J Agric Food Chem 2019; 67: 625–36. doi: 10.1021/acs.jafc.8b06209

  105. Wang G, Fu XL, Wang JJ, Guan R, Sun Y, Tony To SS. Inhibition of glycolytic metabolism in glioblastoma cells by Pt3glc combinated with PI3K inhibitor via SIRT3-mediated mitochondrial and PI3K/Akt-MAPK pathway. J Cell Physiol 2019; 234: 5888–903. doi: 10.1002/jcp.26474

  106. Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci 2008; 4: 89–96.

  107. Jeandet P, Bessis R, Maume BF, Meunier P, Peyron D, Trollat P. Effect of enological practices on the resveratrol isomer content of wine. J Agric Food Chem 1995; 43: 316–9. doi: 10.1021/Jf00050a010

  108. Maruyama H, Kawakami F, Lwin TT, Imai M, Shamsa F. Biochemical characterization of ferulic acid and caffeic acid which effectively inhibit melanin synthesis via different mechanisms in B16 melanoma cells. Biol Pharm Bull 2018; 41: 806–10. doi: 10.1248/bpb.b17-00892

  109. Rosendahl AH, Perks CM, Zeng L, Markkula A, Simonsson M, Rose C, et al. Caffeine and caffeic acid inhibit growth and modify estrogen receptor and insulin-like growth factor I receptor levels in human breast cancer. Clin Cancer Res 2015; 21: 1877–87. doi: 10.1158/1078-0432.CCR-14-1748

  110. Tyszka-Czochara M, Bukowska-Strakova K, Kocemba-Pilarczyk KA, Majka M. Caffeic acid targets AMPK signaling and regulates tricarboxylic acid cycle anaplerosis while metformin downregulates HIF-1alpha-induced glycolytic enzymes in human cervical squamous cell carcinoma lines. Nutrients 2018; 10: 841. doi: 10.3390/nu10070841

  111. Zhang X, Lin D, Jiang R, Li H, Wan J, Li H. Ferulic acid exerts antitumor activity and inhibits metastasis in breast cancer cells by regulating epithelial to mesenchymal transition. Oncol Rep 2016; 36: 271–8. doi: 10.3892/or.2016.4804

  112. Wang T, Gong X, Jiang R, Li H, Du W, Kuang G. Ferulic acid inhibits proliferation and promotes apoptosis via blockage of PI3K/Akt pathway in osteosarcoma cell. Am J Transl Res 2016; 8: 968–80. doi:

  113. Gao JH, Yu H, Guo WK, Kong Y, Gu LN, Li Q, et al. The anticancer effects of ferulic acid is associated with induction of cell cycle arrest and autophagy in cervical cancer cells. Cancer Cell Int 2018; 18: 102. doi: 10.1186/S12935-018-0595-Y

  114. Kawabata K, Yamamoto T, Hara A, Shimizu M, Yamada Y, Matsunaga K, et al. Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats. Cancer Lett 2000; 157: 15–21. doi: 10.1016/s0304-3835(00)00461-4

  115. Lukitasari M, Nugroho DA, Widodo N. Chlorogenic acid: the conceivable chemosensitizer leading to cancer growth suppression. J Evid Based Integr Med 2018; 23: 2515690X18789628. doi: 10.1177/2515690X18789628

  116. Wang X, Liu J, Xie Z, Rao J, Xu G, Huang K, et al. Chlorogenic acid inhibits proliferation and induces apoptosis in A498 human kidney cancer cells via inactivating PI3K/Akt/mTOR signalling pathway. J Pharm Pharmacol 2019; 71: 1100–9. doi: 10.1111/jphp.13095

  117. Verma S, Singh A, Mishra A. Gallic acid: molecular rival of cancer. Environ Toxicol Pharmacol 2013; 35: 473–85. doi: 10.1016/j.etap.2013.02.011

  118. Pang JS, Yen JH, Wu HT, Huang ST. Gallic acid inhibited matrix invasion and AP-1/ETS-1-mediated MMP-1 transcription in human nasopharyngeal carcinoma cells. Int J Mol Sci 2017; 108: 1354. doi: 10.3390/ijms18071354

  119. Gong J, Zhou S, Yang S. Vanillic acid suppresses HIF-1 alpha expression via inhibition of mTOR/p70S6K/4E-BP1 and Raf/MEK/ERK pathways in human colon cancer HCT116 cells. Int J Mol Sci 2019; 20: 465. doi: 10.3390/ijms20030465

  120. Pei K, Ou J, Huang J, Ou S. p-Coumaric acid and its conjugates: dietary sources, pharmacokinetic properties and biological activities. J Sci Food Agric 2016; 96: 2952–62. doi: 10.1002/jsfa.7578

  121. Quideau S, Deffieux D, Douat-Casassus C, Pouysegu L. Plant polyphenols: chemical properties, biological activities, and synthesis. Angew Chem Int Ed Engl 2011; 50: 586–621. doi: 10.1002/anie.201000044

  122. Landete JM. Ellagitannins, ellagic acid and their derived metabolites: a review about source, metabolism, functions and health. Food Res Int 2011; 44: 1150–60. doi: 10.1016/j.foodres.2011.04.027

  123. Duan J, Zhan JC, Wang GZ, Zhao XC, Huang WD, Zhou GB. The red wine component ellagic acid induces autophagy and exhibits anti-lung cancer activity in vitro and in vivo. J Cell Mol Med 2019; 23: 143–54. doi: 10.1111/jcmm.13899

  124. Ismail T, Calcabrini C, Diaz AR, Fimognari C, Turrini E, Catanzaro E, et al. Ellagitannins in cancer chemoprevention and therapy. Toxins 2016; 8: 151. doi: 10.3390/toxins8050151

  125. Heber D. Multitargeted therapy of cancer by ellagitannins. Cancer Lett 2008; 269: 262–8. doi: 10.1016/j.canlet.2008.03.043

  126. Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D. Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells. J Agric Food Chem 2006; 54: 980–5. doi: 10.1021/jf052005r

  127. Kasimsetty SG, Bialonska D, Reddy MK, Ma G, Khan SI, Ferreira D. Colon cancer chemopreventive activities of pomegranate ellagitannins and urolithins. J Agric Food Chem 2010; 58: 2180–7. doi: 10.1021/jf903762h

  128. Kwon HY, Kim JH, Kim B, Srivastava SK, Kim SH. Regulation of SIRT1/AMPK axis is critically involved in gallotannin-induced senescence and impaired autophagy leading to cell death in hepatocellular carcinoma cells. Archiv Toxicol 2018; 92: 241–57. doi: 10.1007/s00204-017-2021-y

  129. Nemec MJ, Kim H, Marciante AB, Barnes RC, Talcott ST, Mertens-Talcott SU. Pyrogallol, an absorbable microbial gallotannins-metabolite and mango polyphenols (Mangifera Indica L.) suppress breast cancer ductal carcinoma in situ proliferation in vitro. Food Funct 2016; 7: 3825–33. doi: 10.1039/c6fo00636a

  130. RomeroPerez AI, LamuelaRaventos RM, Waterhouse AL, delaTorreBoronat MC. Levels of cis- and trans-resveratrol and their glucosides in white and rose Vitis vinifera wines from Spain. J Agric Food Chem 1996; 44: 2124–8. doi: 10.1021/Jf9507654

  131. Lamuelaraventos RM, Romeroperez AI, Waterhouse AL, Delatorreboronat MC. Direct Hplc analysis of Cis-resveratrol and trans-resveratrol and piceid isomers in Spanish red vitis-vinifera wines. J Agric Food Chem 1995; 43: 281–3. doi: 10.1021/Jf00050a003

  132. Rauf A, Imran M, Butt MS, Nadeem M, Peters DG, Mubarak MS. Resveratrol as an anti-cancer agent: a review. Crit Rev Food Sci Nutr 2018; 58: 1428–47. doi: 10.1080/10408398.2016.1263597

  133. Leonard SS, Xia C, Jiang BH, Stinefelt B, Klandorf H, Harris GK, et al. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun 2003; 309: 1017–26. doi: 10.1016/j.bbrc.2003.08.105

  134. Kode A, Rajendrasozhan S, Caito S, Yang SR, Megson IL, Rahman I. Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 2008; 294: L478–88. doi: 10.1152/ajplung.00361.2007

  135. Okada H, Mak TW. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat Rev Cancer 2004; 4: 592–603. doi: 10.1038/nrc1412

  136. Liao PC, Ng LT, Lin LT, Richardson CD, Wang GH, Lin CC. Resveratrol arrests cell cycle and induces apoptosis in human hepatocellular carcinoma Huh-7 cells. J Med Food 2010; 13: 1415–23. doi: 10.1089/jmf.2010.1126

  137. Aziz MH, Nihal M, Fu VX, Jarrard DF, Ahmad N. Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3’-kinase/Akt pathway and Bcl-2 family proteins. Mol Cancer Ther 2006; 5: 1335–41. doi: 10.1158/1535-7163.MCT-05-0526

  138. Benitez DA, Hermoso MA, Pozo-Guisado E, Fernandez-Salguero PM, Castellon EA. Regulation of cell survival by resveratrol involves inhibition of NF kappa B-regulated gene expression in prostate cancer cells. Prostate 2009; 69: 1045–54. doi: 10.1002/pros.20953

  139. Colin D, Limagne E, Jeanningros S, Jacquel A, Lizard G, Athias A, et al. Endocytosis of resveratrol via lipid rafts and activation of downstream signaling pathways in cancer cells. Cancer Prevent Res 2011; 4: 1095–106. doi: 10.1158/1940-6207.CAPR-10-0274

  140. Su JL, Yang CY, Zhao M, Kuo ML, Yen ML. Forkhead proteins are critical for bone morphogenetic protein-2 regulation and anti-tumor activity of resveratrol. J Biol Chem 2007; 282: 19385–98. doi: 10.1074/jbc.M702452200

  141. Kim YA, Lee WH, Choi TH, Rhee SH, Park KY, Choi YH. Involvement of p21WAF1/CIP1, pRB, Bax and NF-kappaB in induction of growth arrest and apoptosis by resveratrol in human lung carcinoma A549 cells. Int J Oncol 2003; 23: 1143–9. doi: 10.1136/bjo.2007.132290

  142. Whyte L, Huang YY, Torres K, Mehta RG. Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res 2007; 67: 12007–17. doi: 10.1158/0008-5472.CAN-07-2464

  143. Ahmad N, Adhami VM, Afaq F, Feyes DK, Mukhtar H. Resveratrol causes WAF-1/p21-mediated G(1)-phase arrest of cell cycle and induction of apoptosis in human epidermoid carcinoma A431 cells. Clin Cancer Res 2001; 7: 1466–73.

  144. Ko JH, Sethi G, Um JY, Shanmugam MK, Arfuso F, Kumar AP, et al. The role of resveratrol in cancer therapy. Int J Mol Sci 2017; 18: 2589. doi: 10.3390/ijms18122589

  145. Limagne E, Thibaudin M, Euvrard R, Berger H, Chalons P, Vegan F, et al. Sirtuin-1 activation controls tumor growth by impeding Th17 differentiation via STAT3 deacetylation. Cell Rep 2017; 19: 746–59. doi: 10.1016/j.celrep.2017.04.004

  146. Vergara D, Valente CM, Tinelli A, Siciliano C, Lorusso V, Acierno R, et al. Resveratrol inhibits the epidermal growth factor-induced epithelial mesenchymal transition in MCF-7 cells. Cancer Lett 2011; 310: 1–8. doi: 10.1016/j.canlet.2011.04.009

  147. Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res 2011; 71: 1263–71. doi: 10.1158/0008-5472.CAN-10-2907

  148. Delmas D, Limagne E, Ghiringhelli F, Aires V. Immune Th17 lymphocytes play a critical role in the multiple beneficial properties of resveratrol. Food Chem Toxicol 2020; 137: 111091. doi: 10.1016/j.fct.2019.111091

  149. Zhang Y, Yang S, Yang Y, Liu T. Resveratrol induces immunogenic cell death of human and murine ovarian carcinoma cells. Infect Agents Cancer 2019; 14: 27. doi: 10.1186/s13027-019-0247-4

  150. Yang Y, Paik JH, Cho D, Cho JA, Kim CW. Resveratrol induces the suppression of tumor-derived CD4+CD25+ regulatory T cells. Int Immunopharmacol 2008; 8: 542–7. doi: 10.1016/j.intimp.2007.12.006

  151. Verdura S, Cuyas E, Cortada E, Brunet J, Lopez-Bonet E, Martin-Castillo B, et al. Resveratrol targets PD-L1 glycosylation and dimerization to enhance antitumor T-cell immunity. Aging 2020; 12: 8–34. doi: 10.18632/aging.102646

  152. Valentovic MA. Evaluation of resveratrol in cancer patients and experimental models. Adv Cancer Res 2018; 137: 171–88. doi: 10.1016/bs.acr.2017.11.006

How to Cite
Duan J., Guo H., Fang Y., & Zhou G. (2021). The mechanisms of wine phenolic compounds for preclinical anticancer therapeutics. Food & Nutrition Research, 65.
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