Characterization of the Effects of Different Retinoids on the Growth and Differentiation of a Human Melanoma Cell Line and Selected Subclones1

The effect of four different retinoids [retinol, 13-c/s-retinoic acid (Ro4-3780), /8-all-irans-retinoic acid, and aromatic retinoie acid ethyl ester (Ro10-9359)] on the cellular proliferation (cell number) and biochemical differentiation (tyrosinase activ ity) of a human melanoma cell line (MIRW) and three subclones was assessed. All four retinoids (10~6 M) inhibited the cellular proliferation (36 to 42%) and stimulated tyrosinase activity (58 to 72%) in the parent cell line to a similar extent. In contrast, the effects of the different retinoids on three derived melanoma clones was dissimilar. For example, in clone A6, ß-a\\-transretinoic acid stimulated tyrosinase activity by 48% but caused only a 7% inhibition of cellular proliferation. This retinoid caused a more pronounced effect in the other two subclones, stimulating tyrosinase from 135 to 195% and inhibiting growth 19 to 33%. All three melanoma clones demonstrated increased tyrosinase activity (110 to 225%) and reduced proliferation (37 to 52%) following exposure to 13-c/s-retinoic acid. This retinoid was found overall to be the most effective stimulator of tyrosin ase, while retinol was observed to be the least active, stimulat ing enzyme activity slightly (25%) in only one of three clones. Retinol inhibited proliferation 27 to 33% in two of three mela noma subclones. The aromatic retinoic acid ethyl ester ele vated tyrosinase levels in two clones but inhibited the enzyme in one melanoma line. Cellular proliferation, however, was reduced in all three clones. These results suggest that retinoidinduced changes in human melanoma cell growth and differ entiation reflect underlying cellular differences and diverse biochemical interactions.