Alteration of melanoma melanogenesis by phenotypic modifiers

Human melanoma cells (MM96E) were incubated with a phenotypic modifier (L-ethionine) to compare its effects on phenotypic expression with those induced by sodium butyrate and dimethyl sulfoxide. In contrast to the latter agents, L-ethionine (8mM) failed to arrest the cell cycle at the G1 phase or to inhibit colony formation ability after 48 hr incubation. Tyrosinase activity changed in parallel with 5-S-cysteinyldopa (5-S-CD) content during treatment with sodium butyrate or dimethyl sulfoxide. Tyrosinase was inhibited in L-ethionine-treated cells, probably because of metabolism of L-ethionine to sulfhydryl compounds; this remains to be clarified. Gamma-glutamyl transpeptidase activity changed inversely with tyrosinase activity after sodium butyrate or dimethyl sulfoxide incubation, whereas L-ethionine did not significantly alter the enzyme activity. In addition, only sodium butyrate induced alkaline phosphatase activity. L-ethionine was less effective than sodium butyrate or dimethyl sulfoxide in inhibiting expression of the B8G3 melanosomal antigen, as determined by Western blotting. These results suggest that phenotypic modifiers (differentiation inducers) affect melanoma cells in various ways and that melanogenesis therefore reflects only one aspect of differentiation in pigment cells.