Inhibition of clonogenic growth of melanoma cells by combination of melanocyte stimulating hormone and theophylline.

The combination of MSH and theophylline is synergistic in inhibiting the growth as well as stimulating the differentiation of pigmented melanoma cells. In order to determine if a permanent alteration in the proliferative potential of these cells was achieved, we examined the effect of MSH and theophylline alone and in combination upon the plating efficiency and tumorigenicity of S-91 Cloudman melanoma cells. Following treatment with the combination of MSH and theophylline, the cells became deeply pigmented and had their colony forming ability reduced to 28% of control. Neither MSH or theophylline alone, although effective in reducing the growth rate of the cells, caused a significant reduction in clonogenic growth. When cells were pretreated with MSH and theophylline alone or in combination and reinjected into mice, the combination of MSH and theophylline caused a significant reduction in percentage of animals developing tumor (reduced to 14% of control). Cells treated with either MSH or theophylline alone were similar in their tumorigenic potential to control cells. These effects were selective since the nonmelanocytic control cells, mouse fibroblast L929 and Chinese hamster ovary when treated similarly did not exhibit any alteration in their clonogenic potential. The treatment of responsive cells with the combination of MSH and theophylline is capable of causing permanent decrease in the proliferative potential of murine melanoma cells and may have relevance to the treatment of this disease in man.