Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1745, Issue 1, Pages 111-123Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2004.12.004
Keywords
agmatine; polyamine; cell cycle; cyclin A; cyclin B-1; metabolism
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Putrescine, spermidine and spermine are low molecular polycations that play important roles in cell growth and cell cycle progression of normal and malignant cells. Agmatine (1-amino-4-guanidobutane), another polyamine formed through arginine decarboxylation, has been reported to act as an antiproliferative agent in several non-intestinal mammalian cell models. Using the human colon adenocarcinoma HT-29 Glc(-/+) cell line, we demonstrate that agmatine, which markedly accumulated inside the cells without being metabolised, exerted a strong cytostatic effect with an IC50 close to 2 mM. Agmatine decreased the rate of L-ornithine decarboxylation and induced a 70% down-regulation of ornithine decarboxylase (ODC) expression. Agmatine caused a marked decrease in putrescine and spermidine cell contents, an increase in the N-1-acetylspermidine level without altering the spermine pool. We show that agmatine induced the accumulation of cells in the S and G(2)/M phases, reduced the rate of DNA synthesis and decreased cyclin A and B I expression. We conclude that the anti-metabolic action of agmatine on HT-29 cells is mediated by a reduction in polyamine biosynthesis and induction in polyamine degradation. The decrease in intracellular polyamine contents, the reduced rate of DNA synthesis and the cell accumulation in the S phase are discussed from a causal perspective. (c) 2005 Elsevier B.V All rights reserved.
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