EFFECTS OF TOCOPHEROL (VITAMIN-E) ACID SUCCINATE ON MORPHOLOGICAL ALTERATIONS AND GROWTH-INHIBITION IN MELANOMA-CELLS IN CULTURE

Abstract

The effects of various forms of tocopherol (vitamin E) on the growth and differentiation of mouse melanoma (B-16) and mouse fibroblast (L-cells) cells in culture were studied. D-.alpha.-tocopherol acid succinate induced morphological alterations and growth inhibition in melanoma cells. When vitamin E acid succinate was removed 4 days after treatment, the above changes remained irreversible for a period of 24 h, after which resistant cells and partially affected cells renewed cell division and eventually reached confluency. The relative efficacy of D and DL forms of vitamin E acid succinate remains to be evaluated. Other forms of vitamin E such as DL-.alpha.-tocopherol free alcohol, Aquasol DL-.alpha.-tocopherol acetate, DL-.alpha.-tocopherol nicotinate or sodium succinate with an equivalent volume of ethanol, at similar concentrations, were ineffective. Vitamin E acid succinate at similar concentrations did not induce morphological changes in fibroblasts. Melanoma cells were about 2-fold more sensitive to vitamin E acid succinate than were fibroblasts for the criterion of growth inhibition. Vitamin E acid succinate-induced morphological changes and growth inhibition in melanoma cells were also expressed in hormone-supplemented serum-free medium but the concentration requirement was about 5 times less than that needed in serum-supplemented medium. Although cAMP-stimulating agents cause growth inhibition and morphological changes in melanoma cells in culture, vitamin E acid succinate-induced morphological alterations in melanoma cells are not mediated by a rise in cAMP. Ethanol was sufficient to increase the melanin content in melanoma cells. Vitamin E acid succinate may be a potentially useful tumor therapeutic agent.