In Vitro Modulation of Proliferation and Melanization of S91 Melanoma Cells by Prostaglandins1

The effects of prostaglandins (PCs) on the ( loudman S91 melanoma CCL 53.1 cell line indicate that melanogenesis and proliferation are regulated by separate mechanisms that are not necessarily cyclic AMP (cAMP) dependent. These cells responded to PGEi and PGE2 in a dosedependent manner, by an increase of tyrosinase activity and by inhibition of proliferation. PGAi and PGD2 inhibited cellular proliferation and tyrosinase activity, while PGF¿,had no effect after 24 h of treatment. PGE,, but not PGEj or l'(,I),, increased cellular cAMP levels after 30 min of treatment. Treatment with 10 Mg/ml PGE, inhibited cellular proliferation after 4 h and enhanced tyrosinase activity after 12 h. Tyrosinase stimulation by PGEi required de novo transcription and translation. Actinomycin D, cycloheximide, and the tyrosinase inhibitor phenylthiocarbamide blocked tyrosinase activation but did not alter the inhibitory effect of PGEi on proliferation. Dibutyryl cAMP and 3isobutyl-1-methylxanthine augmented tyrosinase activation by PGEi without enhancing the inhibitory action of PGEi on cell growth. Neither blockage nor enhancement of the PGEi effect on tyrosinase altered the PGEi-induced retardation of proliferation. These results are in marked contrast to the traditional concept that elevation of cAMP levels in melanoma cells necessarily results in stimulation of melanogenesis and inhibition of proliferation. The data presented propose independent and possibly alternative pathways for the regulation of these two cellular events.