Antiproliferative effects of dietary phenolic substances and hydrogen peroxide

There has been controversy as to whether the antiproliferative activity of dietary phenolic substances on cancer cells is due to the bioactivities of phenolics or the generation of hydrogen peroxide (H2O2) in media as an artifact. This study was to investigate whether the formation of H2O2 by different phenolics induces acute toxicity and carcinogenicity in normal rat liver epithelial cells. Gallic acid, one of the major antioxidants present in fruits and vegetables, dose-dependently generated considerably more H2O2 in DMEM media without cells than did quercetin. Gallic acid exerted stronger antiproliferative activity than quercetin on both Caco-2 human colon cancer cells (Caco-2 cells) and WB-F344 normal rat liver epithelial cells (WB cells) cultured in DMEM media, and the effect was partially reduced by catalase. Furthermore, gallic acid (but not quercetin) also inhibited gap-junction intercellular communication (GJIC; a carcinogenic phenomenon), which was in part protected by the addition of catalase. Exogenous H2O2 addition also inhibited the proliferation of both Caco-2 cells and WB cells and inhibited GJIC in a dose-dependent manner, but these effects were almost abolished by the treatment with catalase. From these results it is concluded that the antiproliferative effects of some antioxidants on cancer cells are partially due to their prooxidant actions.