In vitro modulation of proliferation and melanization of S91 melanoma cells by prostaglandins.
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 alpha 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 micrograms/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.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone; D066298:In Vitro Techniques; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors; D015230:Prostaglandin D2; D011453:Prostaglandins / Q000494:pharmacology*; D011454:Prostaglandins A / Q000494:pharmacology; D011457:Prostaglandins D / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology
D008543:Melanins; D011453:Prostaglandins; D011454:Prostaglandins A; D011457:Prostaglandins D; D011458:Prostaglandins E; D003609:Dactinomycin; D003994:Bucladesine; D003513:Cycloheximide; D014442:Monophenol Monooxygenase; D000527:Alprostadil; D015232:Dinoprostone; D015230:Prostaglandin D2; D015056:1-Methyl-3-isobutylxanthine; C100573:prostaglandin A1