Abstract A96: Trans-resveratrol decreases breast proliferation and alters mammary promoter hypermethylation in women at increased risk for breast cancer

Abstract

Abstract Trans-resveratrol, present in high concentration in the skin of red grapes and red wine, has a dose-dependent antiproliferative effect in vitro, prevents the formation of mammary tumors, and has been touted as a chemopreventive agent. We conducted in vitro experiments in hormone sensitive breast cancer cells and observed that trans-resveratrol downregulated DNA methyltransferase gene expression in a dose dependent fashion. Based upon this preclinical observation, we determined if transresveratrol had dose related anti-proliferative and methylation effects in humans. 16 adult women at increased breast cancer risk were randomized in double-blind fashion to placebo, 5 or 50 mg trans-resveratrol twice daily for 12 weeks. We collected serum, breast nipple aspirate fluid (NAF) and mammary duct (MD) specimens from all participants at all time points. Breast specific and systemic antiproliferative effects were assessed measuring the cancer promoting prostaglandin (PG)E2 in NAF and serum as well as changes in MD cytology, while methylation assessment of three cancer related genes (p16, RASSF-1α, APC) was performed on MD specimens. Serum resveratrol increased after consuming both trans-resveratrol doses (p<.001 for both). Cytology was not significantly changed by resveratrol treatment. RASSF-1α methylation significantly decreased after high (but not low) dose resveratrol, and the decrease correlated with increasing levels of serum resveratrol. RASSF-1α methylation also correlated with change in NAF levels of PGE2 (p=.0087). This work provides novel insights into the anticancer effects of trans-resveratrol in women at increased breast cancer risk, including prostaglandin inhibition and a decrease in methylation of the tumor suppressor gene RASSF-1α. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A96.