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

  • Authors:
    • Francine Gossé
    • Stamatiki Roussi
    • Sylvain Guyot
    • Angèle Schoenfelder
    • André Mann
    • Jean-Pierre Bergerat
    • Nikolaus Seiler
    • Francis Raul
  • View Affiliations

  • Published online on: August 1, 2006     https://doi.org/10.3892/ijo.29.2.423
  • Pages: 423-428
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Abstract

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-L-methionine decarboxylase, key enzymes of polyamine biosynthesis, and they induce spermidine/spermine N1-acetyltransferase, which initiates retroconversion of poly-amines. 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 PAO-catalysed 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.

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August 2006
Volume 29 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Gossé F, Roussi S, Guyot S, Schoenfelder A, Mann A, Bergerat J, Seiler N and Raul F: Potentiation of apple procyanidin-triggered apoptosis by the polyamine oxidase inactivator MDL 72527 in human colon cancer-derived metastatic cells. Int J Oncol 29: 423-428, 2006.
APA
Gossé, F., Roussi, S., Guyot, S., Schoenfelder, A., Mann, A., Bergerat, J. ... Raul, F. (2006). Potentiation of apple procyanidin-triggered apoptosis by the polyamine oxidase inactivator MDL 72527 in human colon cancer-derived metastatic cells. International Journal of Oncology, 29, 423-428. https://doi.org/10.3892/ijo.29.2.423
MLA
Gossé, F., Roussi, S., Guyot, S., Schoenfelder, A., Mann, A., Bergerat, J., Seiler, N., Raul, F."Potentiation of apple procyanidin-triggered apoptosis by the polyamine oxidase inactivator MDL 72527 in human colon cancer-derived metastatic cells". International Journal of Oncology 29.2 (2006): 423-428.
Chicago
Gossé, F., Roussi, S., Guyot, S., Schoenfelder, A., Mann, A., Bergerat, J., Seiler, N., Raul, F."Potentiation of apple procyanidin-triggered apoptosis by the polyamine oxidase inactivator MDL 72527 in human colon cancer-derived metastatic cells". International Journal of Oncology 29, no. 2 (2006): 423-428. https://doi.org/10.3892/ijo.29.2.423