[Utilization of melanin precursors for experimental chemotherapy of malignant melanoma].
Melanin synthesis is a metabolic pathway unique and specific to melanocytes. It occurs by conversion of tyrosine to dopa and dopaquinone in the presence of tyrosinase. It is highly accelerated in malignant melanoma with a marked increase of tyrosinase activity. This study summarizes the recent progress in experimental chemotherapeutic approaches to malignant melanoma by utilizing melanin precursors, and presents our current results. Our studies indicated (a) that hydroquinone and 4-isopropylcatechol are selectively toxic to melanocytes and melanoma cells, (b) that their actions are mediated through tyrosinase, and (c) that dopa is selectively and highly incorporated into melanoma cells and melanocytes depending on the tyrosinase activity. In addition, our new compounds, i.e., 4-S-cysteinylphenol and 4-S-cysteaminylphenol were highly toxic to melanoma cells, increasing the life span of B16 melanoma bearing mice and decreasing melanoma growth in C57 BL mice. Other synthetic compounds, e.g., cysteinylcatechols and their devivatives, were, however, not toxic to melanoma cells. 4-S-cysteinylphenol and 4-S-cysteaminylphenol appeared to exert their cytotoxicity through the action of tyrosinase present in melanoma cells, thus providing a kind of "guided missile" approach to melanoma chemotherapy.
D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003545:Cysteine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004295:Dihydroxyphenylalanine / Q000494:pharmacology; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D002395:Catecholamines; D008543:Melanins; D003543:Cysteamine; D004295:Dihydroxyphenylalanine; C043036:4-S-cysteinylphenol; D014442:Monophenol Monooxygenase; C043037:4-S-cysteaminylphenol; D003545:Cysteine