Resveratrol modulates human mammary epithelial cell O-acetyltransferase, sulfotransferase, and kinase activation of the heterocyclic amine carcinogen N-hydroxy-PhIP

Resveratrol (trans-3,4′,5-trihydroxystilbene) is a natural antioxidant found in plants, such as grapes, that studies suggest has cancer chemopreventive activity. We investigated the effects of resveratrol on DNA binding via esterification reactions with 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP) – a metabolite of a mammary gland carcinogen present in cooked meats. Treatment of primary cultures of human mammary epithelial cells with 50 μM resveratrol led to a decrease in PhIP-DNA adducts ranging from 31 to 69%. Using substrate-specific assays and mammary gland tissue cytosols, resveratrol inhibited PhIP-DNA adduct formation by O-acetyltransferase and sulfotransferase catalysis. Cytosols from tumor tissue and breast reduction tissue were similarly affected. Resveratrol also suppressed O-acetyltransferase and sulfotransferase activities from the breast cancer cell lines MCF-7 and ZR-75-1. It was also observed that resveratrol stimulated ATP-dependent cytosolic activation of N-OH-PhIP in all human samples but not in mouse liver samples. In addition to resveratolʹs other preventive effects, the present data suggest that O-acetyltransferases and sulfotransferases may represent anti-oncogenic targets for resveratrol.