Polyphenols as cancer chemopreventive agents

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Abstract
This article summarizes available data on the chemopreventive efficacies of tea polyphenols, curcumin and ellagic acid in various model systems. Emphasis is placed upon the anticarcinogenic activity of these polyphenols and their proposed mechanism(s) of action. Tea is grown in about 30 countries and, next to water, is the most widely consumed beverage in the world. Tea is manufactured as either green, black, or oolong; black tea represents approximately 80% of tea products. Epidemiological studies, though inconclusive, suggest a protective effect of tea consumption on human cancer. Experimental studies of the antimutagenic and anticarcinogenic effects of tea have been conducted principally with green tea polyphenols (GTPs). GTPs exhibit antimutagenic activity in vitro, and they inhibit carcinogen‐induced skin, lung, forestomach, esophagus, duodenum and colon tumors in rodents. In addition, GTPs inhibit TPA‐induced skin tumor promotion in mice. Although several GTPs possess anticarcinogenic activity, the most active is (–)‐epigallocatechin‐3‐gallate (EGCG), the major constituent in the GTP fraction. Several mechanisms appear to be responsible for the tumor‐inhibitory properties of GTPs, including enhancement of antioxidant (glutathione peroxidase, catalase and quinone reductase) and phase II (glutathione‐S‐transferase) enzyme activities; inhibition of chemically induced lipid peroxidation; inhibition of irradiation‐and TPA‐induced epidermal ornithine decarboxylase (ODC) and cyclooxygenase activities; inhibition of protein kinase C and cellular proliferation; antiinflammatory activity; and enhancement of gap junction intercellular communication. Curcumin is the yellow coloring agent in the spice turmeric. It exhibits antimutagenic activity in the Ames Salmonella test and has anticarcinogenic activity, inhibiting chemically induced preneoplastic lesions in the breast and colon and neoplastic lesions in the skin, forestomach, duodenum and colon of rodents. In addition, curcumin inhibits TPA‐induced skin tumor promotion in mice. The mechanisms for the anticarcinogenic effects of curcumin are similar to those of the GTPs. Curcumin enhances glutathione content and glutathione‐S‐transferase activity in liver; and it inhibits lipid peroxidation and arachidonic acid metabolism in mouse skin, protein kinase C activity in TPA‐treated NIH 3T3 cells, chemically induced ODC and tyrosine protein kinase activities in rat colon, and 8‐hydroxyguanosine formation in mouse fibroblasts. Ellagic acid is a polyphenol found abundantly in various fruits, nuts and vegetables. Ellagic acid is active in antimutagenesis assays, and has been shown to inhibit chemically induced cancer in the lung, liver, skin and esophagus of rodents, and TPA‐induced tumor promotion in mouse skin. Ellagic acid functions through a variety of mechanisms, including inhibition of microsomal P‐450 enzymes, stimulation of glutathione‐S‐transferase, scavenging the reactive metabolites of carcinogens, and direct binding to DNA, thus potentially masking sites that would normally interact with ultimate carcinogens. GTP, curcumin and ellagic acid exhibit potent antioxidant effects. This property, coupled with their other effects, make them effective chemopreventives against both the initiation and promotion/progression stages of carcinogenesis.

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