Modulation of growth in normal and malignant melanocytic cells by all-trans retinoic acid

Human epidermal melanocytes were examined for proliferation under various conditions in the presence or absence of all-trans retinoic acid (RA). Under conditions which supported proliferation, RA at concentrations of 0.25-1.0 microgram/ml inhibited cell growth but was not cytotoxic. When melanocytes were cultured under conditions which by themselves did not support growth, RA did not overcome the growth limitation. Treatment of melanocytes with RA altered their morphological appearance. Alterations included retraction of dendritic processes, increased flattening, and a slight darkening of the cytoplasm in some of the cells. However, when examined biochemically, there was no significant change in the amount of malanin per cell or in tyrosinase activity. RA also inhibited proliferation of six different malignant melanoma lines. Inhibition was observed over the same RA concentrations and over the same time course in the melanoma cells as was seen in melanocytes. Inhibition of melanocyte and melanoma cell proliferation was slowly reversed following removal of RA from the culture medium. These results indicate that RA can inhibit proliferation of melanocytic cells.