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

The University of Cincinnati College of Medicine, Department of Dermatology, Cincinnati, Ohio 45267-0592

The effects of prostaglandins (PGs) on the Cloudman 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 PGE₁ and PGE₂ in a dose-dependent manner, by an increase of tyrosinase activity and by inhibition of proliferation. PGA₁ and PGD₂ inhibited cellular proliferation and tyrosinase activity, while PGF₂ had no effect after 24 h of treatment. PGE₁, but not PGE₂ or PGD₂, increased cellular cAMP levels after 30 min of treatment. Treatment with 10 µg/ml PGE₁ inhibited cellular proliferation after 4 h and enhanced tyrosinase activity after 12 h. Tyrosinase stimulation by PGE₁ 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 PGE₁ on proliferation. Dibutyryl cAMP and 3-isobutyl-1-methylxanthine augmented tyrosinase activation by PGE₁ without enhancing the inhibitory action of PGE₁ on cell growth. Neither blockage nor enhancement of the PGE₁ effect on tyrosinase altered the PGE₁-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.

¹ Supported in part by The National Institute of Arthritis, Diabetes, and Digestion and Kidney Diseases (Grant AM25252), the Elma Margaret Lapp Foundation, and the Dermatology Foundation.

² To whom requests for reprints should be addressed, at University of Cincinnati College of Medicine, Department of Dermatology, 231 Bethesda Avenue, Mail Location 592, Cincinnati, OH 45267.

Received 12/ 3/86. Revised 3/16/87. Accepted 3/25/87.

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