Resveratrol, a polyphenol found primarily in grapes, berries, and nuts, has been found to inhibit the growth of both hormone receptor positive (ER+/PR+) and hormone receptor (ER-/PR-) breast cancer cells, without being toxic to normal cells. While resveratrol is a phytoestrogen, it exerts chemopreventive effects through multiple pathways.
Resveratrol has also been shown to increase the effectiveness of a variety of breast cancer treatments, including radiotherapy, aromatase inhibitors, the chemotherapy drugs Taxol (paclitaxel), Taxotere (docetaxel), Adriamycin (doxorubicin), Cisplatin, and Alkeran (Melphalan), as well as the epidermal growth factor receptor (EGFR) inhibitor Iressa (gefitinib).
In addition, resveratrol has been shown to reduce Adriamycin-induced cardiomyopathy (heart muscle damage that can result in heart failure). Now a new study has reported how resveratrol enhances the therapeutic effects of Adriamycin.
Best food sources of resveratrol
Red grapes and purple grape juice, blueberries, and cranberries all have high resveratrol content and have also been found to associated with reduced breast cancer risk. Other foods with significant levels of resveratrol include strawberries, peanuts, and pistachio nuts. Blackberries and raspberries also contain some resveratrol. Red wine is a well known source of resveratrol. However, drinking red wine has been shown to be harmful for breast cancer patients, on balance, as a result of its alcohol content.
Resveratrol supplements are not recommended
Safe and effective dosages of resveratrol supplements have not been established. Cell and animal studies suggest that taking resveratrol in concentrated form could have unintended adverse effects, including potentially increasing the rate of proliferation, migration, and invasion of breast cancer cells at some dosage levels.
One study reported that resveratrol alone promoted mammary tumor growth and metastasis in a mouse model of ER- breast cancer whereas it inhibited it in combination with quercetin and catechin (other grape polyphenols). Another study found that supplementation with zinc plus resveratrol in a rat model of breast cancer substantially increased the rate of carcinogenesis and the number of carcinogen-induced mammary tumors.
Efforts are under way to develop drugs based on resveratrol that can be used to increase the potency of chemotherapy. In the mean time, we urge those undergoing breast cancer treatment to obtain resveratrol by consuming foods rather than taking it in supplement form.
Latest research shows how resveratrol enhances the cytotoxicity of Adriamycin
The study referenced at the beginning of this news story was designed to find proteins in hormone receptor positive MCF-7 breast cancer cells that are affected by resveratrol in a way that suggests enhanced chemopreventive or treatment effects. The authors observed significant changes in the expression of a total of 16 proteins in resveratrol-treated MCF-7 cells, including heat shock protein 27 (HSP27).
HSP27 overexpression has been associated with inhibition of cancer cell apoptosis (programmed cell death) and resistance to cancer treatment. The authors first showed that resveratrol induced apoptosis in MCF-7 cells. They then evaluated the chemosensitization effect of increasing concentrations of resveratrol in combination with Adriamycin in MCF-7 breast cancer cells, demonstrating that resveratrol effectively sensitized MCF-7 cells to the treatment. Finally, the authors evaluated the role of HSP27 inhibition in treatment effectiveness, finding that HSP27 inhibition enhanced the cytotoxicity of Adriamycin.
The authors conclude that resveratrol could potentially improve the therapeutic effects of Adriamycin. In addition, altering HSP27 levels using natural agents such as resveratrol might be an effective adjuvant in breast cancer therapy.
Please see our article on breast cancer diet during Adriamycin chemotherapy for more information on how to optimize treatment and reduce side effects.
Selected breast cancer studies
Both aerobic exercise and resveratrol supplementation attenuate doxorubicin-induced cardiac injury in mice
Dolinsky VW, Rogan KJ, Sung MM, Zordoky BN, Haykowsky MJ, Young ME, et al. Both aerobic exercise and resveratrol supplementation attenuate doxorubicin-induced cardiac injury in mice. American Journal of Physiology-Endocrinology and Metabolism. American Physiological Society; 2013; 305:E243-E253 10.1152/ajpendo.00044.2013
Resveratrol decreases breast cancer cell viability and glucose metabolism by inhibiting 6-phosphofructo-1-kinase
Gomez LS, Zancan P, Marcondes MC, Ramos-Santos L, Meyer-Fernandes JR, Sola-Penna M, et al. Resveratrol decreases breast cancer cell viability and glucose metabolism by inhibiting 6-phosphofructo-1-kinase. Biochimie. Elsevier BV; 2013; 95:1336-1343 10.1016/j.biochi.2013.02.013
Dietary grape polyphenol resveratrol increases mammary tumor growth and metastasis in immunocompromised mice
Castillo-Pichardo L, Cubano LA, Dharmawardhane S. Dietary grape polyphenol resveratrol increases mammary tumor growth and metastasis in immunocompromised mice. BMC Complementary and Alternative Medicine. Springer Science and Business Media LLC; 2013; 13 10.1186/1472-6882-13-6
Protective effects of resveratrol on cisplatin-dependent inner-ear damage in rats
Şimşek G, Tokgoz SA, Vuralkan E, Caliskan M, Besalti O, Akin I. Protective effects of resveratrol on cisplatin-dependent inner-ear damage in rats. European Archives of Oto-Rhino-Laryngology. Springer Science and Business Media LLC; 2012; 270:1789-1793 10.1007/s00405-012-2183-4
Grape Polyphenols Inhibit Akt/Mammalian Target of Rapamycin Signaling and Potentiate the Effects of Gefitinib in Breast Cancer
Castillo-Pichardo L, Dharmawardhane SF. Grape Polyphenols Inhibit Akt/Mammalian Target of Rapamycin Signaling and Potentiate the Effects of Gefitinib in Breast Cancer. Nutrition and Cancer. Informa UK Limited; 2012; 64:1058-1069 10.1080/01635581.2012.716898
Resveratrol induces downregulation of DNA repair genes in MCF-7 human breast cancer cells
Leon-Galicia I, Diaz-Chavez J, Garcia-Villa E, Uribe-Figueroa L, Hidalgo-Miranda A, Herrera LA, et al. Resveratrol induces downregulation of DNA repair genes in MCF-7 human breast cancer cells. European Journal of Cancer Prevention. Ovid Technologies (Wolters Kluwer Health); 2013; 22:11-20 10.1097/cej.0b013e328353edcb
Abstract 5676: Effects of resveratrol on paclitaxel-sensitive and -resistant triple negative breast cancer cells
Sprouse AA, Herbert B. Abstract 5676: Effects of resveratrol on paclitaxel-sensitive and -resistant triple negative breast cancer cells. Experimental and Molecular Therapeutics. American Association for Cancer Research; 2012; 10.1158/1538-7445.am2012-5676