Resveratrol

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This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.

Modes of action

“As a naturally occurring small molecule, resveratrol has been shown to be capable of mediating cancer therapy via targeting multiple pathways involving cancer initiation, promotion and progression.”¹Xiao Q, Zhu W et al. A review of resveratrol as a potent chemoprotective and synergistic agent in cancer chemotherapy. Frontiers in Pharmacology. 2019 Jan 9;9:1534; Zhang L, Wen X, Li M, Li S, Zhao H. Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene. Biofactors. 2018 Jan;44(1):61-68. Resveratrol targets the Notch signaling pathway in glioblastoma cell lines.²Gersey Z, Osiason AD et al. Therapeutic targeting of the notch pathway in glioblastoma multiforme. World Neurosurgery. 2019 Nov;131:252-263.e2. One review highlights the role and related molecular mechanisms of resveratrol in cancer treatment, focusing on the role of resveratrol in the tumor microenvironment and the sensitization of cancer cells for chemotherapy and radiotherapy.³Jiang Z, Chen K et al. Resveratrol and cancer treatment: updates. Annals of the New York Academy of Sciences. 2017 Sep;1403(1):59-69.

“The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R.”⁴Majumdar AP, Banerjee S et al. Curcumin synergizes with resveratrol to inhibit colon cancer. Nutrition and Cancer. 2009;61(4):544-53.

Preclinical evidence

Notable preclinical evidence is presented here; clinical evidence is summarized in How can resveratrol help you? What the research says ›

Resveratrol protected against the toxicity induced by carcinogenic substances including benzo[a]pyrene, azoxymethane, and DMBA in animal studies.⁵Xiao Q, Zhu W et al. A review of resveratrol as a potent chemoprotective and synergistic agent in cancer chemotherapy. Frontiers in Pharmacology. 2019 Jan 9;9:1534. 

Improving treatment outcomes

Brain cancer

Resveratrol has decreased glioma tumor volumes,⁶Luís Â, Marcelino H, Domingues F, Pereira L, Cascalheira JF. Therapeutic potential of resveratrol for glioma: a systematic review and meta-analysis of animal model studies. International Journal of Molecular Sciences. 2023 Nov 22;24(23):16597. induced apoptosis, and inhibited angiogenesis and tumor invasion in brain cancer.⁷Andrade S, Ramalho MJ, Pereira MDC, Loureiro JA. Resveratrol brain delivery for neurological disorders prevention and treatment. Frontiers in Pharmacology. 2018 Nov 20;9:1261.

Breast cancer

Resveratrol reversed multidrug resistance in breast cancer cell studies.⁸Alamolhodaei NS, Tsatsakis AM, Ramezani M, Hayes AW, Karimi G. Resveratrol as MDR reversion molecule in breast cancer: an overview. Food and Chemical Toxicology. 2017 May;103:223-232; Hu Y, Li C, Li H, Li M, Shu X. Resveratrol-mediated reversal of tumor multi-drug resistance. Current Drug Metabolism. 2014;15(7):703-10.

Colorectal cancer

Resveratrol inhibited the proliferation of colon cancer cells,⁹Chen H, Jin ZL, Xu H. MEK/ERK signaling pathway in apoptosis of SW620 cell line and inhibition effect of resveratrol. Asian Pacific Journal of Tropical Medicine. 2016 Jan;9(1):49-53. induced apoptosis and inhibited cell cycle progression of colon cancer cells.¹⁰Fajardo AM, Piazza GA. Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2015 Jul 15;309(2):G59-70; Mahyar-Roemer M, Köhler H, Roemer K. Role of Bax in resveratrol-induced apoptosis of colorectal carcinoma cells. BMC Cancer. 2002 Oct 17;2:27; Vanamala J, Radhakrishnan S, Reddivari L, Bhat VB, Ptitsyn A. Resveratrol suppresses human colon cancer cell proliferation and induces apoptosis via targeting the pentose phosphate and the talin-FAK signaling pathways—a proteomic approach. Proteome Science. 2011 Aug 17;9(1):49. It also sensitized colon cancer cells to 5-fluorouracil.¹¹Santandreu FM, Valle A, Oliver J, Roca P. Resveratrol potentiates the cytotoxic oxidative stress induced by chemotherapy in human colon cancer cells. Cell Physiology and Biochemistry. 2011;28(2):219-28.

Gynecological cancer

Resveratrol increased growth inhibitory/anticancer activity of cisplatin and doxorubicin in cells.¹²Rezk YA, Balulad SS, Keller RS, Bennett JA. Use of resveratrol to improve the effectiveness of cisplatin and doxorubicin: study in human gynecologic cancer cell lines and in rodent heart. American Journal of Obstetrics and Gynecology. 2006 May;194(5):e23-6.

Lung cancer

Resveratrol inhibited cancer cell proliferation and induced cell cycle arrest and apoptosis in lung cancer cells.¹³Yousef M, Vlachogiannis IA, Tsiani E. Effects of resveratrol against lung cancer: in vitro and in vivo studies. Nutrients. 2017 Nov 10;9(11). pii: E1231.

Ovarian cancer

Resveratrol has shown anticancer effects in ovarian cancer cell studies: reduced cell growth and metabolism¹⁴Tino AB, Chitcholtan K2, Sykes PH, Garrill A. Resveratrol and acetyl-resveratrol modulate activity of VEGF and IL-8 in ovarian cancer cell aggregates via attenuation of the NF-κB protein. Journal of Ovarian Research. 2016 Dec 1;9(1):84; Zhong LX, Nie JH, Liu J, Lin LZ. Correlation of ARHI upregulation with growth suppression and STAT3 inactivation in resveratrol-treated ovarian cancer cells. Cancer Biomarkers. 2018;21(4):787-795. and inhibited ovarian cancer cell migration.¹⁵Ferraresi A, Phadngam S et al. Resveratrol inhibits IL-6-induced ovarian cancer cell migration through epigenetic up-regulation of autophagy. Molecular Carcinogenesis. 2017 Mar;56(3):1164-1181.

Thyroid cancer

Resveratrol showed anticancer effects on thyroid cancer cells.¹⁶Shin HJ, Hwang KA, Choi KC. Antitumor effect of various phytochemicals on diverse types of thyroid cancers. Nutrients. 2019 Jan 9;11(1). pii: E125.

Prostate cancer

Resveratrol shows anticancer effects, including apoptosis in cell studies of prostate cancer.¹⁷Kumar A, Rimando AM, Levenson AS. Resveratrol and pterostilbene as a microRNA-mediated chemopreventive and therapeutic strategy in prostate cancer. Annals of the New York Academy of Sciences. 2017 Sep;1403(1):15-26; Singh SK, Banerjee S, Acosta EP, Lillard JW, Singh R. Resveratrol induces cell cycle arrest and apoptosis with docetaxel in prostate cancer cells via a p53/ p21^WAF1/CIP1 and p27^KIP1 pathway. Oncotarget. 2017 Mar 7;8(10):17216-17228.

Managing side effects

Resveratrol protected against cardiotoxicity from anthracyclines or arsenic trioxide in preclinical studies.¹⁸Xiao Q, Zhu W et al. A review of resveratrol as a potent chemoprotective and synergistic agent in cancer chemotherapy. Frontiers in Pharmacology. 2019 Jan 9;9:1534; Gu J, Hu W, Zhang DD. Resveratrol, a polyphenol phytoalexin, protects against doxorubicin-induced cardiotoxicity. Journal of Cellular and Molecular Medicine. 2015 Oct;19(10):2324-8; Lou Y, Wang Z. et al. Resveratrol prevents doxorubicin-induced cardiotoxicity in H9c2 cells through the inhibition of endoplasmic reticulum stress and the activation of the Sirt1 pathway. International Journal of Molecular Medicine. 2015 Sep;36(3):873-80.

Resveratrol attenuated arsenic trioxide-induced arsenic accumulation, structural abnormalities and arsenic-related toxicity in animal kidneys and liver.¹⁹Xiao Q, Zhu W et al. A review of resveratrol as a potent chemoprotective and synergistic agent in cancer chemotherapy. Frontiers in Pharmacology. 2019 Jan 9;9:1534. It also partially prevented carbon tetrachloride-induced acute liver damage in animals.²⁰Xiao Q, Zhu W et al. A review of resveratrol as a potent chemoprotective and synergistic agent in cancer chemotherapy. Frontiers in Pharmacology. 2019 Jan 9;9:1534. 

Resveratrol protected against indomethacin-induced gastric ulcers in mice at a lower dose (2 mg per kilogram) but delayed healing at a higher dose (10 mg per kilogram).²¹Dey A, Guha P, Chattopadhyay S, Bandyopadhyay SK. Biphasic activity of resveratrol on indomethacin-induced gastric ulcers. Biochemical and Biophysical Research Communications. 2009 Mar 27;381(1):90-5.

Reducing cancer risk

Cancer as a whole

36% lower tumor incidence among cell lines or animals treated with resveratrol in a meta-analysis of preclinical studies²²Feng Y, Zhou J, Jiang Y. Resveratrol in lung cancer—a systematic review. Journal of BUON. 2016 Jul-Aug;21(4):950-953. 

Colorectal cancer

Resveratrol prevented formation of colon tumors and reduced their numbers in mice²³Schneider Y, Duranton B et al. Resveratrol inhibits intestinal tumorigenesis and modulates host-defense-related gene expression in an animal model of human familial adenomatous polyposis. Nutrition and Cancer. 2001;39(1):102-7; Cui X, Jin Y et al. Resveratrol suppresses colitis and colon cancer associated with colitis. Cancer Prevention Research (Philadelphia). 2010 Apr;3(4):549-59. and impaired the growth of colorectal aberrant crypt foci in rats.²⁴Tessitore L, Davit A, Sarotto I, Caderni G. Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21(CIP) expression. Carcinogenesis. 2000 Aug;21(8):1619-22; Sengottuvelan M, Nalini N. Dietary supplementation of resveratrol suppresses colonic tumour incidence in 1,2-dimethylhydrazine-treated rats by modulating biotransforming enzymes and aberrant crypt foci development. British Journal of Nutrition. 2006 Jul;96(1):145-53.

Skin cancer

Resveratrol, including topical application, protected against UVR-induced skin cancer in mice by modulating the proteins that are involved in apoptosis.²⁵Xiao Q, Zhu W et al. A review of resveratrol as a potent chemoprotective and synergistic agent in cancer chemotherapy. Frontiers in Pharmacology. 2019 Jan 9;9:1534.

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