Resveratrol, a natural product derived from grape, exhibits antiestrogenicactivity and inhibits the growth of human breast cancer cells

Resveratrol is a natural phytoalexin compound found in grapes and other foo d products. In this study, the effect of resveratrol on the growth of human breast cancer cells was examined. Results show that resveratrol inhibits t he growth of estrogen receptor(ER)-positive MCF-7 cells in a dose-dependent fashion. Detailed studies with MCF-7 cells demonstrate that resveratrol an tagonized the growth-promoting effect of 17-beta-estradiol (E-2) in a dose- dependent fashion at both the cellular (cell growth) and the molecular (gen e activation) levels. At 5 x 10(-6) M, resveratrol abolished the growth-sti mulatory effect mediated by concentrations of E-2 up to 10(-9) M. The antie strogenic effect of resveratrol could be observed at a concentration of 10- 6 M and above. The antiestrogenic effect of resveratrol was also demonstrat ed at the molecular level. Resveratrol in a dose-dependent fashion antagoni zed the stimulation by E-2 of progesterone receptor gene expression in MCF- 7 cells. Moreover, expression of transforming growth factor-cr. and insulin -like growth factor I receptor mRNA was inhibited while the expression of t ransforming growth factor beta 2 mRNA was significantly elevated in MCF-7 c ells cultivated in the presence of resveratrol (10(-5) M). in summary, our results show that resveratrol, a partial ER agonist itself, acts as an ER a ntagonist in the presence of estrogen leading to inhibition of human breast cancer cells. (C) 1999 Wiley-Liss, Inc.