Potentiation of apple procyanidin-triggered apoptosis by the polyamine oxidase inactivator MDL 72527 in human colon cancer-derived metastatic

Autor: Gossé, Francine, Roussi, Stamatiki, Guyot, Sylvain, Schoenfelder, Angèle, Mann, André, Bergerat, Jean-Pierre, Seiler, Nikolaus, Raul, Françis
Přispěvatelé: ProdInra, Migration, Université Louis Pasteur - Strasbourg I, Station de Recherches Cidricoles et Biotransformation des Fruits et Légumes (SRC - BFL), Institut National de la Recherche Agronomique (INRA), Pharmacochimie de la communication cellulaire (PCC), Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Zdroj: International Journal of Oncology
International Journal of Oncology, Spandidos Publications, 2006, 29, pp.423-426
ISSN: 1019-6439
1791-2423
Popis: International audience; Apple procyanidins have chemopreventive properties in a model of colon cancer, they affect intracellular signalling pathways, and trigger apoptosis in a human adenocarcinoma-derived metastatic cell line (SW620). In the present study we investigated relationships between procyanidin-induced alterations in polyamine metabolism and apoptotic effects. Apple procyanidins diminish the activities of ornithine decarboxylase and S-adenosyl-Lmethionine decarboxylase, key enzymes of polyamine biosynthesis, and they induce spermidine/spermine N1- acetyltransferase, which initiates retroconversion of polyamines. As a consequence of the enzymatic changes polyamine concentrations are diminished, and N1-acetyl-polyamines accumulate in SW620 cells. In contrast with expectations MDL 72527, an inactivator of polyamine oxidase (PAO), improved the anti-proliferative effect of procyanidins, and caused an increase of the proportion of apoptotic cells, although it prevented the formation of hydrogen peroxide and 3-acetamidopropanal, the cytotoxic products of PAOcatalysed degradation of N1-acetylspermidine and N1- acetylspermine. Addition of 500 μM N1-acetylspermidine to the culture medium in the presence of procyanidins mimicked the effect of MDL 72527. Therefore we presume that the enhanced procyanidin-triggered apoptosis by MDL 72527 is mediated by the accumulation of N1-acetyl-polyamines. The observation that apple procyanidins enhance polyamine catabolism and reduce polyamine biosynthesis activity similar to known inducers of SSAT, without sharing their toxicity, and the potentiation of these effects by low concentrations of MDL 72527 suggests apple procyanidins for chemopreventive and therapeutic interventions.
Databáze: OpenAIRE
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