POLYPHENOLS AS CANCER CHEMOPREVENTIVE AGENTS

This article summarizes available data on the chemopreventive efficaci es of tea polyphenols, curcumin and ellagic acid in various model syst ems. Emphasis is placed upon the anticarcinogenic genic activity of th ese polyphenols and their proposed mechanism(s) of action. Tea is grow n in about 30 countries and, next to water, is the most widely consume d beverage in the world. Tea is manufactured as either green, black, o r oolong; black tea represents approximately 80% of tea products. Epid emiological studies, though inconclusive, suggest a protective effect of tea consumption on human cancer. Experimental studies of the antimu tagenic and anticarcinogenic effects of tea have been conducted princi pally with green tea polyphenols (GTPs). GTPs exhibit antimutagenic ac tivity in vitro, and they inhibit carcinogen-induced skin, lung, fores tomach, esophagus, duodenum and colon tumors in rodents. In addition, GTPs inhibit TPA-induced skin tumor promotion in mice. Although severa l GTPs possess anticarcinogenic activity, the most active is (-)-epiga llocatechin-3-gallate (EGCG), the major constituent in the GTP fractio n. Several mechanisms appear to be responsible for the tumor-inhibitor y properties of GTPs, including enhancement of antioxidant (glutathion e peroxidase, catalase and quinone reductase) and phase II (glutathion e-S-transferase) enzyme activities; inhibition of chemically induced l ipid peroxidation; inhibition of irradiation- and TPA-induced epiderma l ornithine decarboxylase (ODC) and cyclooxygenase activities; inhibit ion of protein kinase C and cellular proliferation; antiinflammatory a ctivity; and enhancement of gap junction intercellular communication. Curcumin is the yellow coloring agent in the spice turmeric. It exhibi ts antimutagenic activity in the Ames Salmonella test and has anticarc inogenic activity, inhibiting chemically induced preneoplastic lesions in the breast and colon and neoplastic lesions in the skin, forestoma ch, duodenum and colon of rodents. In addition, curcumin inhibits TPA- induced skin tumor promotion in mice. The mechanisms for the anticarci nogenic effects of curcumin are similar to those of the GTPs. Curcumin enhances glutathione content and glutathione-S-transferase activity i n liver; and it inhibits lipid peroxidation and arachidonic acid metab olism in mouse skin, protein kinase C activity in TPA-treated NIH 3T3 cells, chemically induced ODC and tyrosine protein kinase activities i n rat colon, and 8-hydroxyguanosine formation in mouse fibroblasts. El lagic acid is a polyphenol found abundantly in various fruits, nuts an d vegetables. Ellagic acid is active in antimutagenesis assays, and ha s been shown to inhibit chemically induced cancer in the lung, Liver, skin and esophagus of rodents, and TPA-induced tumor promotion in mous e skin. Ellagic acid functions through a variety of mechanisms, includ ing inhibition of microsomal P-450 enzymes, stimulation of glutathione -S-transferase, scavenging the reactive metabolites of carcinogens, an d direct binding to DNA, thus potentially masking sites that would nor mally interact with ultimate carcinogens. GTP, curcumin and ellagic ac id exhibit potent antioxidant effects. This property, coupled with the ir other effects, make them effective chemopreventives against both th e initiation and promotion/progression stages of carcinogenesis. (C) 1 995 Wiley-Liss, Inc.