Methylthiopropylamine, a potent inhibitor of spermidine synthase and its antiproliferative effect on human lymphoid leukemia Molt 4B cells

The catalytic activity of spermidine synthase isolated from rat ventral prostate was significantly inhibited by methylthiopropylamine (MTPA). Spermine synthase was almost insensitive to this inhibitor. Inhibition of spermidine synthase by MTPA was competitive with respect to a substrate putrescine (Ki, 3.3 = 10(-7) M), but not competitive with another substrate decarboxylated S-adenosylmethionine (dec AdoMet). MTPA inhibited the growth of human lymphoid leukemia Molt 4B cells. The spermidine content in the inhibitor-treated cells was dose-dependently depressed, whereas the putrescine content was increased concomitantly. In these spermidine depleted and growth retarded Molt 4B cells, the synthesis of protein, but not of DNA or RNA, was found to be significantly diminished.