Selective toxicity of 5-S-cysteinyldopa, a melanin precursor, to tumor cells in vitro and in vivo.
The effect of 5-S-cysteinyl-L-3,4-dihydroxyphenylalanine (cys-dopa), an intermediate in the pathway from L-3,4-dihydroxyphenylalanine (L-dopa) to pheomelanin, on the growth of eight human tumor cell lines in culture was compared to that of L-dopa. The tumor cell lines tested comprise two neuroblastomas (NB-1 and YT-nu), two amelanotic melanomas (HMV and SEKI), a gastric carcinoma (MKN-28), and three squamous cell carcinomas (HeLa-S3, KB, and a salivary gland carcinoma). Cys-dopa at a concentration of 1 mM inhibited growth of NB-1 (66%), YT-nu (67%), HMV (44%), SEKI (60%), MKN-28 (47%), HeLa-S3 (24%), KB (64%), and salivary gland carcinoma (33%), while L-dopa exhibited similar or even lower degree of inhibition at a concentration of 6 mM. On the other hand, both catechols had little effect on the growth of two fibroblasts derived originally from normal tissues (mouse fibroblast L929 and Chinese hamster fibroblast Don-6). Cys-dopa and L-dopa inhibited DNA and protein synthesis in YT-nu cells, but RNA synthesis was less affected. Treatment with cys-dopa at a dose of 1000 mg/kg i.p. for 7 days prolonged by 50% the life span of mice inoculated with L1210 leukemia. Normal mice given cys-dopa at a dose of 1000 mg/kg for 12 days showed no signs of toxicity. These results suggest the potential of cys-dopa as an antitumor agent.
D000818:Animals; D000970:Antineoplastic Agents; D002460:Cell Line; D003548:Cysteinyldopa / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008543:Melanins / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D011379:Prognosis; D014176:Protein Biosynthesis; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D008543:Melanins; D003548:Cysteinyldopa; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D004247:DNA