The killing effect of 4-S-cysteaminylphenol, a newly synthesised melanin precursor, on B16 melanoma cell lines.
We have examined the killing effect of 4-S-cysteaminylphenol (4-S-CAP), a newly synthesised melanin precursor, on B16 melanoma cell lines possessing different melanin-producing activities and found it to be particularly effective in heavily melanised melanoma cells, but less so in moderately melanised melanoma cells, and having no effect on amelanotic melanoma cells and nonmelanoma cells. Thus, it was found that the killing effect of 4-S-CAP is highly dependent upon the synthesis of melanin and tyrosinase in melanoma cells, suggesting that 4-S-CAP may become toxic to melanoma cells only after oxidation by tyrosinase. The killing activity of 4-S-CAP also was found to be associated with a profound inhibition of the thymidine incorporation in pigmented melanoma cells, as compared to the uridine and leucine incorporation. Further, the inhibition of DNA synthesis was most pronounced in heavily melanised melanoma cells, less so in moderately melanised melanoma cells, and not seen in amelanotic melanoma cells. As a possible mechanism that might account for this action, it may be that 4-S-CAP is oxidised by tyrosinase to the o-quinone form via the catechol derivative and that some of the quinones then conjugate with sulfhydryl enzymes including DNA polymerase, thus exerting a killing activity for pigmented melanoma cells. Thus, 4-S-CAP appears to provide a new, effective cytotoxic agent for rational chemotherapy of malignant melanomas.
Yamada
I
I
Department of Radiology, School of Medicine, Tokyo Medical and Dental University, Japan.
Seki
S
S
Ito
S
S
Suzuki
S
S
Matsubara
O
O
Kasuga
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003543:Cysteamine / Q000494:pharmacology* / Q000031:analogs & derivatives; D004247:DNA / Q000096:biosynthesis; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D019384:Nucleic Acid Synthesis Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D008543:Melanins; D019384:Nucleic Acid Synthesis Inhibitors; D003543:Cysteamine; D004247:DNA; C043037:4-S-cysteaminylphenol