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 wa s comparable to etoposide in terms of IC50 value. The cell death observed f rom both CHEN-spm and etoposide was typically apoptotic with increased DNA fragmentation, altered cell morphology, and cell cycle distribution. CPEN-s pm, on the other hand, exhibited no toxic effects over the short-team (24 h ) exposure period. Intracellular polyamine content decreased in the presenc e of all inhibitors but only CPEN-spm produced significant induction of spe rmidine/spermine N-1-acetyltransferase in 24 h. Thus, increased polyamine c atabolism appears not to be essential for the initiation of apoptotic cell death in these human leukemic cells. (C) 2000 Wiley-Liss, Inc.