Cytotoxicity of novel unsymmetrically substituted inhibitors of polyamine biosynthesis in human cancer cells.

The cytotoxicity of two novel polyamine analogues was compared with that of a known cytotoxic drug, etoposide, in a human promyelogenous leukemic cell line. CHEN-spm showed significant acute cytotoxicity in these cells and was comparable to etoposide in terms of IC(50) value. The cell death observed from both CHEN-spm and etoposide was typically apoptotic with increased DNA fragmentation, altered cell morphology, and cell cycle distribution. CPEN-spm, on the other hand, exhibited no toxic effects over the short-term (24 h) exposure period. Intracellular polyamine content decreased in the presence of all inhibitors but only CPEN-spm produced significant induction of spermidine/spermine N(1)-acetyltransferase in 24 h. Thus, increased polyamine catabolism appears not to be essential for the initiation of apoptotic cell death in these human leukemic cells.