Mechanism of growth inhibition of melanoma cells by 4-S-cysteaminylphenol and its analogues.
Our previous studies have shown that 4-S-cysteaminylphenol (4-S-CAP) causes a significant inhibition of in vivo melanoma growth and a marked depigmentation of black skin and hair follicles. These studies have suggested a role of tyrosinase in the manifestation of these in vivo effects. In this study 4-S-CAP and its analogues were examined for their effects on the growth of human melanoma cells in vitro. 4-S-CAP and 4-S-HomoCAP exhibited strong cytotoxicity with effects much greater than those of alpha-methyl-4-S-CAP and N,N-dimethyl-4-S-CAP. The cytotoxicity of the former two amines was completely prevented by semicarbazide, an inhibitor of plasma monoamine oxidase, while that of the latter two was not prevented by semicarbazide, catalase, and phenylthiourea, a tyrosinase inhibitor. In culture medium 4-S-CAP was rapidly converted by the action of monoamine oxidase present in fetal bovine serum to the aldehyde which was then metabolized to the alcohol and the carboxylic acid when cells were present. alpha-Methyl-4-S-CAP was found to exert higher cytotoxicity to cells with higher tyrosinase activity and melanin content. These results suggest that the in vitro cytotoxicity of 4-S-CAP and 4-S-HomoCAP is mediated through conversion to the aldehydes while that of alpha-methyl-4-S-CAP appears to be dependent on tyrosinase activity to some extent.
Inoue
S
S
Institute for Comprehensive Medical Science, School of Hygiene, Fujita Health University, Toyoake, Japan.
Ito
S
S
Wakamatsu
K
K
Jimbow
K
K
Fujita
K
K
D000970:Antineoplastic Agents / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003543:Cysteamine / Q000378:metabolism / Q000494:pharmacology / Q000031:analogs & derivatives; D006801:Humans; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010670:Phenylthiourea / Q000494:pharmacology; D012663:Semicarbazides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008543:Melanins; D008996:Monoamine Oxidase Inhibitors; D012663:Semicarbazides; C010059:carbamylhydrazine; D003543:Cysteamine; D010670:Phenylthiourea; D014442:Monophenol Monooxygenase; D008995:Monoamine Oxidase; C043037:4-S-cysteaminylphenol