Prostaglandin-independent effects of aspirin on cell cycle and putrescine synthesis in human colon carcinoma cells
| Autor: | S Camous, François Blachier, C Mayeur, M Andriamihaja, G Charpigny, E Eklou-Kalonji, Véronique Robert, P Reinaud |
|---|---|
| Přispěvatelé: | Laboratoire de nutrition et sécurité alimentaire, Institut National de la Recherche Agronomique (INRA), Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), ProdInra, Migration |
| Rok vydání: | 2003 |
| Předmět: |
Ornithine
Physiology Colorectal cancer [SDV]Life Sciences [q-bio] Cell chemistry.chemical_compound 0302 clinical medicine Polyamines ComputingMilieux_MISCELLANEOUS 0303 health sciences biology Chemistry Anti-Inflammatory Agents Non-Steroidal Cell Cycle General Medicine Cell cycle CANCER 3. Good health [SDV] Life Sciences [q-bio] Isoenzymes medicine.anatomical_structure Biochemistry 030220 oncology & carcinogenesis Colonic Neoplasms HT29 Cells Prostaglandin [INFO] Computer Science [cs] Adenocarcinoma 03 medical and health sciences Physiology (medical) medicine Putrescine Anticarcinogenic Agents Humans [INFO]Computer Science [cs] 030304 developmental biology Pharmacology Aspirin Cell growth Cell Membrane Membrane Proteins medicine.disease Eicosanoid Cell culture Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases biology.protein Cancer research Cyclooxygenase 1 Prostaglandins Cyclooxygenase Caco-2 Cells |
| Zdroj: | Canadian Journal of Physiology and Pharmacology Canadian Journal of Physiology and Pharmacology, NRC Research Press, 2003, 81 (5), pp.443-450 |
| ISSN: | 0008-4212 1205-7541 |
| Popis: | Aspirin consumption has been reported to be able to reduce colorectal cancer risk in humans and in animal models of colon carcinogenesis. Although the mechanism involved in such an effect is not yet clear, both prostaglandin-dependent and -independent effects have been proposed. Using HT-29 Glc/+cells, which originate from a human colon adenocarcinoma, we demonstrated in this study a dose-dependent effect of millimolar concentration of aspirin on cell growth that was concomitant with a rapid accumulation of the cells in the Go/G1 phase, followed by an accumulation in the G2/M phase and by a minor increase in the proportion of cells undergoing nuclear condensation. Cell membrane integrity and cell release into the culture medium were not affected by this treatment. The aspirin effects were apparently unrelated to prostaglandin biosynthesis inhibition, since although these cells were found to express high levels of cyclooxygenase 1 (COX-1) and low levels of COX-2 proteins, they did not produce any measurable net amounts of prostaglandins, based on both utilization of radiolabelled arachidonic acid and the radioimmunoassay of prostaglandins E2 and F2α. In contrast, we identified polyamine biosynthesis as a cellular target of aspirin, since the treatment of HT-29 Glc/+ cells with aspirin reduced the flux of L-ornithine through ornithine decarboxylase, an effect that could not be explained by an acute action of the drug on the ornithine decarboxylase catalytic activity. Since polyamine biosynthesis is strictly necessary for HT-29 cell growth, our data suggest that reduced flux through ornithine decarboxylase may participate in the antiproliferative activity of aspirin towards colonic tumoral cells. It is concluded that in HT-29 Glc/+ cells that are not functional for prostaglandin production, aspirin can affect cell growth, cell cycle, and polyamine biosynthesis without affecting cell membrane integrity.Key words: aspirin, HT-29 cells, cell cycle, prostaglandins, polyamines. |
| Databáze: | OpenAIRE |
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