We have analyzed the effects of various human
interferons produced in bacteria and the antileukemic compound
mezerein (MEZ) on growth and melanogenesis in human
melanoma cells. In four human
melanoma cell lines, recombinant human
fibroblast interferon (IFN-beta) was more active than recombinant human leukocyte
interferons (IFN-alpha A,
IFN-alpha D, or IFN-alpha A/D (Bgl] in inhibiting cellular proliferation. When monolayer cultures were exposed to 1000 IU/ml IFN-beta for four days the degree of growth inhibition in the different
melanoma cell lines varied between 94 and 26%. Similarly, four days growth in medium containing 10 ng/ml MEZ resulted in either no inhibition of growth or as much as 53% inhibition of growth, depending on the specific
melanoma cell line tested. MEZ induced dendrite-like processes, cytoplasmic projections morphologically similar to those normally found in neurons and melanocytes, in all four
melanoma cell lines, whereas none of the
interferons tested had this effect. The combination of
interferon and MEZ resulted in a dramatic inhibition in cellular proliferation in all four
melanoma cell lines. When
cell extracts were assayed for
melanin content, a marker of
melanoma cell differentiation, the combination of IFN-beta and MEZ resulted in higher levels of
melanin than with either agent alone. Dendrite-like formation was also prominent in the cultures treated with this combination. These results indicate that the antiproliferative effect of
interferon toward human
melanoma dells can be enhanced by treatment with MEZ and that this effect is associated with an enhancement of terminal differentiation.