The effects of histamine H2 receptor antagonists on melanogenesis and cellular proliferation in melanoma cells in culture.
B16-C3 murine melanoma, A375P human melanotic melanoma, and C32 human amelanotic melanoma cells were incubated in the presence of (0-4 mM) H2-antagonists, ranitidine and cimetidine. Cell proliferation, tyrosinase activity and melanin content were monitored. H2-antagonists stimulated tyrosinase activity and melanin accumulation in B16-C3 cells in a dose- and time-dependent manner. Stimulation of enzyme activity and pigment production was accompanied by inhibition of cellular proliferation in B16-C3 cells. The inhibitory concentration of cimetidine was approximately 2-fold higher than that of ranitidine. H2-antagonists failed to stimulate melanogenesis in A375P or C32 cells, but inhibited cellular proliferation in both cell lines. These results are the first demonstration of H2-antagonist induced phenotypic changes in malignant melanoma cells in vitro, and represent a novel mechanism for the previously described in vivo antitumor effects of these agents.
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Department of Medicine, State University of New York, Buffalo 14215.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002927:Cimetidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008543:Melanins / Q000032:analysis / Q000096:biosynthesis*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology*
D008543:Melanins; D002927:Cimetidine; D011899:Ranitidine; D014442:Monophenol Monooxygenase