Effect of Vitamin E (DL-α-Tocopherol) on the Growth of the Rat Glioma Cells in Culture

Effects of vitamin E (DL-α-tocopherol) on the growth inhibition, the inhibition of colony formation, and the morphological change of three rat glioma cell lines (RG-12, C-6, and 9L cells) were evaluated in tissue culture. Moreover, the combined efficacies of vitamin E and several chemotherapeutic agents on the survival fraction of 9L glioma cells were studied using the colony-forming assay. Significant growth inhibitory effects appeared with the addition of vitamin E to three rat glioma cell cultures, with dose-dependency at concentrations ranging from 5 to 50 μg/ml of vitamin E. Effective dose (ED50) was 15 μg/ml for RG-12 cells, 17.2 μg/ml for C-6 cells, and 28.0 μg/ml for 9L cells. Regrowth curve analysis of glioma cells following 48 hour administration of vitamin E showed reversible change in growth of glioma cells. The addition of vitamin E to the exponentially growing cultures caused morphological changes in glioma cells, which became visible as early as 24 hours after its administration. The glioma cell processes treated with vitamin E became more elongated than those of untreated cells. Colony-forming assay for evaluation of the combined efficacy of vitamin E and several chemotherapeutic agents showed a significant synergistic effect of vitamin E on the cytotoxicity of vincristine sulfate to 9L cells, which was also dose-dependent to vincristine sulfate and/or vitamin E concentrations (P<0.01). Vitamin E (20 μg/ml) showed only an additive effect on the cytotoxicities of ACNU, bleomycin, and 5-fluorouracil to 9L cells. In conclusion, vitamin E showed a significant synergistic effect on the cytotoxicity of vincristine sulfate to 9L cells. Although the mechanism of this synergistic effect was unknown, more detailed in vitro and in vivo analyses should prove useful in the treatment of malignant gliomas with vitamin E.