Effect of Resveratrol on the Expression of Autocrine Growth Modulators in Human Breast Cancer Cells

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Abstract
The effect of resveratrol on the growth of human breast cancer cells was examined. Resveratrol inhibited the growth of estrogen receptor-positive MCF-7 cells cultivated in the presence of estradiol in a dose-dependent fashion. At 10(-5) M, resveratrol maximally inhibited the growth stimulatory effect mediated by 10(-9) M estradiol without affecting cell viability. At the molecular level, resveratrol in a dose-dependent fashion antagonized the stimulation by estradiol of an estrogen response element reporter gene construct and of progesterone receptor gene expression in MCF-7 cells. Resveratrol also inhibited the proliferation of the estrogen-receptor negative human breast carcinoma cell line MDA-MB-468. These later data suggest that resveratrol can also inhibit breast cancer cell proliferation by another mechanism besides estrogen receptor antagonism. We show here that resveratrol altered the expression of several autocrine growth modulators and their receptors in MCF-7 cells. Resveratrol at 10(-5) M inhibited the expression of the autocrine growth stimulators transforming growth factor-alpha (TGF-alpha), PC cell-derived growth factor, and insulin-like growth factor I receptor mRNA. In addition, resveratrol significantly elevated the expression of the growth inhibitor TGF-beta2 mRNA without changes in TGF-beta1 and TGF-beta3 expression. These data suggest that resveratrol inhibits proliferation by altering autocrine growth modulator pathways in breast cancer cells.