Inhibition of induced melanogenesis in Cloudman melanoma cells by four phenotypic modifiers.
Retinoic acid, hexamethylene bisacetamide, sodium butyrate, and dimethylsulfoxide, four compounds which modulate phenotypic expression in a variety of neoplastic cell lines, all inhibited the induction of tyrosinase activity and melanogenesis by the combination of melanocyte-stimulating hormone and isobutylmethyxanthine in Cloudman S91 melanoma cells. Results were the same in assays of whole cells or in extracts made from them. Only retinoic acid, however, was effective at inhibiting the activation of dopachrome isomerase, another regulatory enzyme in melanogenesis. Despite inhibiting the effects of melanocyte-stimulating hormone (MSH) and isobutylmethylxanthine on tyrosinase activity, all of the agents tested increased the binding of MSH to intact cells. Ultrastructural analysis of treated cells following DOPA cytochemistry revealed that both retinoic acid and hexamethylene bisacetamide arrested melanosomal maturation at stage I-II. Retinoic acid resulted in a derangement of melanosomal structure. The specificity of these agents for preventing the induction of melanogenesis makes them powerful tools for the dissection of this complex cellular process.
Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut 06510.
S J
SJ
Orlow
A K
AK
Chakraborty
R E
RE
Boissy
J M
JM
Pawelek
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D045563:Indolequinones; D007211:Indoles / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism / Q000494:pharmacology; D008544:Melanocytes / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010641:Phenotype; D011809:Quinones / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000081:Acetamides; D002087:Butyrates; D045563:Indolequinones; D007211:Indoles; D008543:Melanins; D011809:Quinones; D020148:Butyric Acid; C001123:dopachrome; D014212:Tretinoin; D009074:Melanocyte-Stimulating Hormones; D014442:Monophenol Monooxygenase; C014026:hexamethylene bisacetamide; D015056:1-Methyl-3-isobutylxanthine; D004121:Dimethyl Sulfoxide