CONTRASTING EFFECTS OF VITAMINS AS MODULATORS OF APOPTOSIS IN CANCER-CELLS AND NORMAL-CELLS - A REVIEW

Individual vitamins can induce direct apoptosis or indirect apoptosis via cell differentiation in cancer cells; however, they can also stimu late antiapoptotic events in certain cancer cells. These effects depen d on the dose, type, and form of vitamins and the type of tumor cells. A mixture of antioxidant vitamins is more effective than individual v itamins, and there is no evidence that such a mixture ever stimulates antiapoptotic events in cancer cells. Vitamins in combination with non vitamin, direct-acting, apoptotic agents (X-rays, chemotherapeutic age nts, and hyperthermia) or in combination with nonvitamin, indirect-act ing, apoptotic agents (adenosine 3',5'-cyclic monophosphate, butyric a cid and interferon) produce a greater extent of apoptotic death in can cer cells in culture. Certain antioxidant vitamins may reduce the effi cacy of some chemotherapeutic agents on rodent fibrosarcoma cells. In contrast to vitamin-induced apoptosis in cancer cells, normal cells ne ver undergo apoptotic death after treatment with vitamins (not includi ng retinoids). On the contrary vitamins protect normal cells against a poptosis induced by a certain group of chemicals. The reasons for this differential effect of vitamins on cancer and normal cells are unknow n. The genetic regulation of apoptosis in cancer cells has not been ad equately defined. Such studies would help in identifying molecular tar gets that can be used to develop effective doses of vitamins or new dr ugs to induce apoptosis selectively in cancer cells.