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 stimulate antiapoptotic events in certain cancer cells. These effects depend on the dose, type, and form of vitamins and the type of tumor cells. A mixture of antioxidant vitamins is more effective than individual vitamins, and there is no evidence that such a mixture ever stimulates antiapoptotic events in cancer cells. Vitamins in combination with nonvitamin, direct-acting, apoptotic agents (X-rays, chemotherapeutic agents, and hyperthermia) or in combination with nonvitamin, indirect-acting, apoptotic agents (adenosine 3',5'-cyclic monophosphate, butyric acid, and interferon) produce a greater extent of apoptotic death in cancer cells in culture. Certain antioxidant vitamins may reduce the efficacy of some chemotherapeutic agents on rodent fibrosarcoma cells. In contrast to vitamin-induced apoptosis in cancer cells, normal cells never undergo apoptotic death after treatment with vitamins (not including retinoids). On the contrary, vitamins protect normal cells against apoptosis induced by a certain group of chemicals. The reasons for this differential effect of vitamins on cancer and normal cells are unknown. The genetic regulation of apoptosis in cancer cells has not been adequately defined. Such studies would help in identifying molecular targets that can be used to develop effective doses of vitamins or new drugs to induce apoptosis selectively in cancer cells.