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

✍ Scribed by Lynsey M. Nairn; Gayle S. Lindsay; P.M. Woster; Heather M. Wallace


Publisher
John Wiley and Sons
Year
2000
Tongue
English
Weight
133 KB
Volume
182
Category
Article
ISSN
0021-9541

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✦ Synopsis


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 1acetyltransferase in 24 h. Thus, increased polyamine catabolism appears not to be essential for the initiation of apoptotic cell death in these human leukemic cells.


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