We previously demonstrated that chemical carcinogens, benzo(a)pyrene and 7, 12-dimethylbenzanthracene efflux mediated by the multidrug resistant (MDR) glycoprotein 170 (P-gp) in our tissue culture cells. The drugs and carcinogen efflux pump, P-gp may serve as an important mechanism in diet- dependent cancer prevention. We further demonstrated that diet-derived flavonols, galangin, quercetin, and kaempferol markedly stimulated the P-gp mediated efflux of benzo(a)pyrene, dimethylbenzanthracene, and adriamycin in human breast cancer MCF-7 and human colon cancer HCT-15 cells. Although P-gp, a product of the mdr gene, is known to play a critical role in cellular resistance to cytotoxic drugs, its function in normal cells has not been defined. We are investigating the mechanism and regulation of P- gp mediated carcinogen efflux by dietary factors in normal tissues as a functional mechanism of diet and cancer prevention. We are examining nutrients and diet-derived constituents in modulating the functional role for increased P-gp expression. We showed that retinoic acid may serve as a substrate for P-gp and enhanced P-gp expression in our tissue culture cells but the functional role of retinoic acid or other related nutrients, e.g. beta-carotene and carcinogen efflux mechanism are not clear. We propose that P-gp mediated carcinogen efflux is regulated by flavonoids, nutrients, and other dietary factors. These nutritional and molecular regulation of P-gp mediated carcinogen efflux mechanisms to cancer prevention are currently under investigation.
