STIMULATION OF MELANOGENESIS IN A HUMAN-MELANOMA CELL-LINE BY RETINOIDS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (9) , 3345-3350
Abstract
Retinoic acid was a potent stimulant of pigmentation in human Hs939 melanoma cells. Exposure to 1 .mu.M retinoic acid for longer than 4 days caused a decrease in the rate of cell proliferation and a concomitant increase in melanogenesis. These effects of retinoic acid progressed linearly in a time-dependent and a dose-dependent fashion, such that at the end of a 7 day treatment cell growth was inhibited by approximately 65%; melanin content and tyrosinase activity increased more than 3-fold over the control. Interpolation of the dose-response curves indicated that 3 nM retinoic acid would cause half-maximal melanogenesis stimulation. No elevation in the level of cAMP was detected in the melanoma cells following various periods of exposure to retinoic acid; the cells were unresponsive to .alpha.-melanocyte-stimulating hormone. In the presence of the tyrosinase inhibitor phenylthiocarbamate, retinoic acid was capable of inhibiting cell proliferation without enhancing melanin synthesis. The tumor promoter phorbol myristate acetate did not affect the proliferation or the differentiation of the Hs939 melanoma cells. The enhancement of melanogenesis by 1 .mu.M retinoic acid was inhibited by 66% in the presence of 0.1 .mu.M phorbol myristate acetate. The tumor promoter did not reverse the growth-inhibitory effect of retinoic acid. Phorbol, a non-tumor promoter, was ineffective. Other retinoids, such as 13-cis-retinoic acid, retinyl acetate and the trimethylmethoxyphenyl analog of retinoic acid, also inhibited the proliferation and enhanced melanin production in the Hs939 cells. Retinyl palmitate, the phenyl analog of retinoic acid, and the pyridyl analog of retinoic acid were ineffective.