Inhibition by polyamines of methylthiopropylamine-induced ornithine decarboxylase in human lymphoid leukemia Molt 4B cells

Methylthiopropylamine (MTPA), an inhibitor of spermidine synthase, markedly induced ornithine decarboxylase (ODC) activity (about 30-fold of the basal level) in human lymphoid leukemia Molt 4B cells. This induction was blocked by the addition of spermidine, spermine or putrescine simultaneously with MTPA. Inhibition by spermidine or spermine of the MTPA-induced ODC activity was larger than that by putrescine. The increase of ODC activity by MTPA led to the large increase of cellular putrescine content. This increase of putrescine content was abolished drastically by the simultaneous addition of spermidine or spermine. The increase of ODC activity was almost completely blocked by the addition of cycloheximide or actinomycin D. This finding suggested that the increase of ODC activity was not due to activation of ODC preformed in Molt 4B cells. The ODC induction by MTPA was dose-dependently blocked by adding the calcium channel blockers (verapamil and nifedipine) or protein kinase C inhibitors (1-(5-isoquinolinesulfonyl)-2-methylpiperazine and palmitoyl carnithine). These results suggested that calcium and protein kinase C (PKC) were involved in MTPA-associated induction of ODC.