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

L M Nairn, G S Lindsay, P M Woster, H M Wallace

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 IC50 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-team (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. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)209-213
Number of pages5
JournalJournal of Cellular Physiology
Volume182
Publication statusPublished - 2000

Keywords

  • SPERMIDINE/SPERMINE N-1-ACETYLTRANSFERASE
  • METHYLGLYOXAL BIS(GUANYLHYDRAZONE)
  • BREAST-CANCER
  • TUMOR-CELLS
  • ANALOGS
  • GROWTH
  • DEATH
  • ACETYLATION
  • INDUCTION

Cite this

Cytotoxicity of novel unsymmetrically substituted inhibitors of polyamine biosynthesis in human cancer cells. / Nairn, L M ; Lindsay, G S ; Woster, P M ; Wallace, H M .

In: Journal of Cellular Physiology, Vol. 182, 2000, p. 209-213.

Research output: Contribution to journalArticle

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abstract = "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 IC50 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-team (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. (C) 2000 Wiley-Liss, Inc.",
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N2 - 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 IC50 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-team (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. (C) 2000 Wiley-Liss, Inc.

AB - 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 IC50 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-team (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. (C) 2000 Wiley-Liss, Inc.

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