Selective cytotoxicity of 4-S-cysteaminylphenol on follicular melanocytes of the black mouse: rational basis for its application to melanoma chemotherapy.
We have previously shown that 4-S-cysteaminylphenol (4-S-CAP) causes a significant inhibition of in vivo melanoma growth. To clarify the mechanism of the in vivo antimelanoma effect, this study evaluated the cellular and subcellular changes of follicular melanocytes after s.c. administration of 4-S-CAP on the lumbar areas of black and albino mice. 4-S-CAP produced a prompt, selective swelling and lysis of melanocytes, resulting eventually in the necrosis of melanocytes and the depigmentation of black hair follicles. None of the degenerative changes were seen in melanocytes and keratinocytes of control albino follicles. Comparison of melanocytes in black and albino follicles revealed that melanin synthesis is highly active in the melanocytes of black follicles while melanin and tyrosinase synthesis is not seen in the melanocytes of albino follicles. The findings indicate that the selective melanocytotoxicity of 4-S-CAP is manifested by lysis and necrosis of cells which are actively engaged in melanin synthesis. 4-S-CAP appears to provide a new modality for rational chemotherapy of malignant melanoma.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006197:Hair / Q000166:cytology / Q000187:drug effects*; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects*; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D014442:Monophenol Monooxygenase / Q000096:biosynthesis
D008543:Melanins; D003543:Cysteamine; D014442:Monophenol Monooxygenase; C043037:4-S-cysteaminylphenol