Stimulation of melanotic expression in murine melanoma cells exposed to polyamine antimetabolites.
An exposure of cultured Cloudman S91 melanoma cells to inhibitors of polyamine biosynthesis, 2-difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) (MGBG), distinctly promoted the expression of differentiated biochemical functions of the tumor cells. Slight to moderate growth inhibition produced by the compounds was associated with a stimulation of melanogenesis, as reflected by a striking enhancement of tyrosinase (EC 1.10.3.1) activity and an increase in cellular melanin content. Both antimetabolites acted synergistically with alpha-melanotropin (MSH), as regards the stimulation of melanogenesis. Exposure of the melanoma cells to MSH resulted in most experiments in a marked decrease of the intracellular polyamine pools, usually involving all three polyamines (putrescine, spermidine and spermine). The DFMO-induced stimulation of melanogenesis was totally suppressed by the administration of putrescine, whereas the MSH-stimulated tyrosinase activity was not influenced by the diamine. Although many recent reports indicate that terminal differentiation is accompanied by a distinct stimulation of polyamine biosynthesis, our results suggest that in certain cells polyamine deprivation may lead to an enhanced expression of differentiated phenotype.
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004357:Drug Synergism; D000518:Eflornithine; D006146:Guanidines / Q000494:pharmacology*; D008543:Melanins / Q000378:metabolism; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D008935:Mitoguazone / Q000494:pharmacology*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011073:Polyamines / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D006146:Guanidines; D008543:Melanins; D011073:Polyamines; D009074:Melanocyte-Stimulating Hormones; D009952:Ornithine; D014442:Monophenol Monooxygenase; D008935:Mitoguazone; D000518:Eflornithine