Effects of Agmatine on Polyamine Metabolism and the Growth of Prostate Tumor Cells

The effects of agmatine on the enzymes responsible for the biosynthesis of polyamines, the resultant levels of polyamines, and their effect on the growth of DU145 human prostate tumor cells were investigated. When agmatine was added to the medium, ornithine decarboxylase (ODC, EC 4.1.1.17) activity was substantially reduced, but S-adenosylmethionine decarboxylase (SAMDC, EC 4.1.1.50) activity increased markedly. These changes in ODC and SAMDC activities were the result of an induction of ODC-antizyme and a decreased turnover rate of SAMDC in the presence of agmatine. Accordingly, there was a decrease in the intracellular levels of putrescine and spermidine but an increase in the intracellular level of spermine. Cell growth was markedly inhibited by agmatine treatment and this inhibition was not recovered by the addition of putrescine or spermidine. Our results suggest that agmatine alters the intracellular amounts of polyamine in the cells, closely related to the inhibition of cell growth.