Polyamine metabolism in Harding-Passey murine melanoma

Abstract

Previous studies have shown that melanoma is very sensitive to inhibitors of polyamine biosynthesis. In this work, we have studied changes in polyamine concentrations and the activities of two key enzymes of their biosynthetic pathway at different stages of growth of Harding-Passey melanoma transplanted to mice. We found that the peak activity of ornithine decarboxylase and S-adenosylmethionine decarboxylase corresponded with maximal rate of tumour growth, but showed no clear correlation with polyamine content of the tumour. The ratio of spermidine to spermine was extremely low, decreasing from 0.80 to 0.46 through the different stages of growth. The half-lives of ornithine decarboxylase and S-adenosylmethionine decarboxylase were 15 and 30 min, respectively. The half-life of melanomal S-adenosylmethionine decarboxylase increased to 110 min in difluoromethylornithine-treated animals. The activities of both decarboxylases were markedly decreased by administration of exogenous polyamines, ornithine decarboxylase being more sensitive than S-adenosylmethionine decarboxylase. Spermidine and spermine were more effective than putrescine or diaminopropane. The results indicate that the melanoma ornithine and S-adenosylmethionine decarboxylases behave in the same way as the enzymes from non-neoplastic tissues.