Polyphenols inhibit promotional phase of tumorigenesis: Relevance of superoxide radicals

Ellagic acid (EA), tannic acid (TA), caffeic acid (CA), and ferulic acid (FA) offer considerable promise as anticarcinogens. The role of these dietary polyphenols was investigated in the promotional phase of carcinogenesis. Topical application of polyphenols simultaneously with phorbol-12-myristate-13-acetate (PMA) or mezerein resulted in significant protection against 7,12-dimethylbenz[a]anthracene-induced skin tumors in mice. Caffeic acid was the most effective inhibitor of tumor promotion. In vivo and in vitro treatment of murine peritoneal macrophages with the tumor promoters resulted in stimulation of superoxide anion radical formation. Tannic acid, caffeic acid, and ferulic acid were stranger inhibitors of PMA- and mezerein-induced superoxide anion radical than ellagic acid in in vivo and in vitro conditions. Treatment of [1(3)-C-14]glycerol- or [methyl-'4C]choline chloride-labeled resident or thioglycollate-elicited macrophages with PMA and mezerein led to accumulation of radioactive diacylglycerol equivalents. The polyphenols were capable of inhibiting these releases.