Vitamin E Enhances the Chemotherapeutic Effects of Adriamycin on Human Prostatic Carcinoma Cells in Vitro

Abstract

Vitamin E (tocopherol) enhances the growth inhibitory effects of adriamycin (ADR) on a variety of cancer cells in vitro. The role of vitamin E (d-.alpha.-tocopheryl) acid succinate in adjuvant chemotherapy with ADR was assessed in DU-145 human prostatic carcinoma cells in culture. Adriamycin produced a dose-dependent growth inhibition of DU-145 cells. The ID50 of DU-145 cells on the criteria: a) of clonal assay was 13 ng./ml. and b) of cell count assay was 14 ng./ml. Vitamin E succinate also inhibited the growth of DU-145 human prostatic carcinoma cells in a dose-dependent manner. 4.4 .mu.g./ml. and 5.4 .mu.g./ml vitamin E succinate in the culture medium produced inhibition of growth to 50 per cent of control (ID50) in the clonal and the cell count assays respectively. When adriamycin and vitamin E succinate were used in combination, both additive and synergistic effects were observed, depending on the concentration of vitamin E succinate used. Doses of vitamin E succinate greater than its ID50 had a synergistic effect while doses smaller than its ID50 had an additive effect. In either, case, the presence of vitamin E succinate caused an enhancement of tumor cell cytotoxicity of adriamycin while decreasing its ID50. Equivalent concentrations of sodium succinate and ethanol used to dissolve vitamin E succinate did not have any effect on DU-145 cells. Thus, it is concluded that the effect of vitamin E succinate is due to vitamin E and not due to succinate or ethanol. These results suggest that vitamin E may have a role in the treatment of human prostatic cancer as an adjuvant agent to adriamycin.