SOME PERSPECTIVES ON DIETARY INHIBITION OF CARCINOGENESIS - STUDIES WITH CURCUMIN AND TEA

Topical application of curcumin inhibits chemically induced carcinogen esis on mouse skin, and oral administration of curcumin inhibits chemi cally induced oral, forestomach, duodenal, and colon carcinogenesis, C urcumin and other inhibitors of cyclooxygenase and lipoxygenase are th ought to inhibit carcinogenesis by preventing the formation of arachid onic acid metabolites, In contrast to our expectation of a tumorigenic effect of arachidonic acid, we found that treatment of 7,12-dimethylb enz[a]anthracene-initiated mouse skin with very high doses of arachido nic acid twice daily, 5 days a week far 26 weeks, failed to result in tumors. We considered the possibility that some of the cancer chemopre ventive effects of curcumin may be related to an effect of this compou nd on cellular differentiation, and we investigated the effect of curc umin on differentiation in the human promyelocytic HL-60 leukemia cell model system. Although curcumin alone had little or no effect on cell ular differentiation, when it was combined with all-trans retinoic aci d or 1 alpha,25-dihydroxyvitamin D-3 a synergistic effect was observed , It Is possible that many dietary chemicals in fruits, vegetables, an d other edible plants can prevent cancer by synergizing with endogenou sly produced stimulators of differentiation such as all-trans retinoic acid, 1 alpha,25-dihydroxyvitamin D-3, and butyrate, More research is needed to test this hypothesis. Administration of green or black tea inhibits carcinogenesis in several animal models, and tumor growth is also inhibited, Several examples were presented of chemopreventive age nts that inhibit carcinogenesis in one animal model but enhance carcin ogenesis in a different animal model, Greater efforts should be made t o understand mechanisms of cancer chemoprevention and to determine whe ther a potential chemopreventive agent is useful in many experimental settings or whether it is useful in only a limited number of experimen tal settings.