Influence of retinoids on growth and melanin content of Harding-Passey-melanoma cells in vitro and B16 transplantable melanoma in vivo.

Growth cessation and cell death of exponentially proliferating Harding-Passey melanoma cells (HPM-73 line) in monolayer culture resulted in the presence of 3.3 X 10(-5) M retinal, while retinol and retinoic acid caused growth retardation at 3.3 X 10(-5) M. Also at 1 X 10(-5) M, the growth-inhibitory effect of retinal was more pronounced than that of retinol or retinoic acid. Following serum removal from the culture media, all 3 retinoids at 3.3 X 10(-6) M or 1 X 10(-5) M revealed cytotoxic effects within 3 days as demonstrated by cell loss from the substratum. Thus, the presence of serum has "protective" effects. Addition of retinal, retinoic acid or retinol at 1 X 10(-5) M to cultures in stationary growth phase did not result in cell loss during period of 6 days. C57Bl mice with B16 melanotic melanoma were i.p. injected during 10 days with retinoids (30 or 100 mcg per mouse daily). All retinoids inhibited B16 tumor growth in vivo. In this respect, retinoic acid was the most effective one. The cellular melanin content of cultured HPM-cells and of B16 melanotic melanoma in vivo was elevated after treatment with retinoids; retinal having the strongest effect.