The mechanism of toxicity of 5-S-cysteinyldopa to tumour cells. Hydrogen peroxide as a mediator of cytotoxicity.
5-S-Cysteinyldopa, a melanin precursor, has been shown to possess selective toxicity to tumour cells in vitro and in vivo. The mechanism of cytotoxicity of the catechol was studied in comparison with L-dopa and 5-S-cysteaminyldopamine. Growth inhibition of human neuroblastoma cell line of YT-nu by 5-S-cysteinyldopa was completely depressed by addition of catalase. Superoxide dismutase and five drugs thought to scavenge hydroxyl radicals or quench singlet oxygen had little effect on the cytotoxicity. Hydrogen peroxide itself was also cytotoxic at low concns. These results indicated that hydrogen peroxide was a mediator of the cytotoxicity of 5-S-cysteinyldopa. It is suggested that reaction of the catechol with cellular superoxide radicals contributes to the production of hydrogen peroxide in addition to autoxidation. Catalase reduced the cytotoxicity of L-dopa by half, while it had no inhibitory effect on the strong cytotoxicity of 5-S-cysteaminyldopamine.
D000818:Animals; D000970:Antineoplastic Agents; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003548:Cysteinyldopa / Q000494:pharmacology* / Q000633:toxicity; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D004298:Dopamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental; D009447:Neuroblastoma; D010084:Oxidation-Reduction
D000970:Antineoplastic Agents; D003548:Cysteinyldopa; D007980:Levodopa; D004295:Dihydroxyphenylalanine; C038667:5-S-cysteaminyldopamine; D006861:Hydrogen Peroxide; D004298:Dopamine