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.