Effect of non-steroidal anti-inflammatory drugs on colon carcinoma Caco-2 cell responsiveness to topoisomerase inhibitor drugs

P. Ricchi, T. Di Matola, G. Ruggiero, D. Zanzi, A. Apicella, A. Di Palma, M. Pensabene, S. Pignata, R. Zarrilli, A. M. Acquaviva

Research output: Contribution to journalArticle

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Abstract

Numerous studies demonstrate that the chemopreventive effect of non-steroidal anti-inflammatory drugs on colon cancer is mediated through inhibition of cell growth and induction of apoptosis. For these effects non-steroidal anti-inflammatory drugs have been recently employed as sensitising agents in chemotherapy. We have shown previously that treatments with aspirin and NS-398, a cyclo-oxygenase-2 selective inhibitor, affect proliferation, differentiation and apoptosis of the human colon adenocarcinoma Caco-2 cells. In the present study, we have evaluated the effects of aspirin and NS-398 non-steroidal anti-inflammatory drugs on sensitivity of Caco-2 cells to irinotecan (CPT II) and etoposide (Vp-16) topoisomerase poisons. We find that aspirin co-treatment is able to prevent anticancer drug-induced toxicity, whereas NS-398 co-treatment poorly affects anticancer drug-induced apoptosis. These effects correlate with the different ability of aspirin and NS-398 to interfere with cell cycle during anticancer drug co-treatment. Furthermore, aspirin treatment is associated with an increase in bcl-2 expression, which persists in the presence of the anticancer drugs. Our data indicate that aspirin, but not NS-398, determines a cell cycle arrest associated with death suppression. This provides a plausible mechanism for the inhibition of apoptosis and increase in survival observed in anticancer drug and aspirin co-treatment.

Original languageEnglish
Pages (from-to)1501-1509
Number of pages9
JournalBritish Journal of Cancer
Volume86
Issue number9
DOIs
Publication statusPublished - May 6 2002

Fingerprint

Topoisomerase Inhibitors
Caco-2 Cells
Aspirin
Colon
Anti-Inflammatory Agents
Carcinoma
Pharmaceutical Preparations
Apoptosis
irinotecan
Therapeutics
Carnitine O-Palmitoyltransferase
Poisons
Etoposide
Prostaglandin-Endoperoxide Synthases
Cell Cycle Checkpoints
Drug-Related Side Effects and Adverse Reactions
Colonic Neoplasms
Cell Cycle
Adenocarcinoma
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide

Keywords

  • Aspirin
  • Bcl-2
  • Cell cycle
  • Colon cancer
  • NS-398
  • Topoisomerase inhibitors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ricchi, P., Di Matola, T., Ruggiero, G., Zanzi, D., Apicella, A., Di Palma, A., ... Acquaviva, A. M. (2002). Effect of non-steroidal anti-inflammatory drugs on colon carcinoma Caco-2 cell responsiveness to topoisomerase inhibitor drugs. British Journal of Cancer, 86(9), 1501-1509. https://doi.org/10.1038/sj.bjc.6600289

Effect of non-steroidal anti-inflammatory drugs on colon carcinoma Caco-2 cell responsiveness to topoisomerase inhibitor drugs. / Ricchi, P.; Di Matola, T.; Ruggiero, G.; Zanzi, D.; Apicella, A.; Di Palma, A.; Pensabene, M.; Pignata, S.; Zarrilli, R.; Acquaviva, A. M.

In: British Journal of Cancer, Vol. 86, No. 9, 06.05.2002, p. 1501-1509.

Research output: Contribution to journalArticle

Ricchi, P, Di Matola, T, Ruggiero, G, Zanzi, D, Apicella, A, Di Palma, A, Pensabene, M, Pignata, S, Zarrilli, R & Acquaviva, AM 2002, 'Effect of non-steroidal anti-inflammatory drugs on colon carcinoma Caco-2 cell responsiveness to topoisomerase inhibitor drugs', British Journal of Cancer, vol. 86, no. 9, pp. 1501-1509. https://doi.org/10.1038/sj.bjc.6600289
Ricchi, P. ; Di Matola, T. ; Ruggiero, G. ; Zanzi, D. ; Apicella, A. ; Di Palma, A. ; Pensabene, M. ; Pignata, S. ; Zarrilli, R. ; Acquaviva, A. M. / Effect of non-steroidal anti-inflammatory drugs on colon carcinoma Caco-2 cell responsiveness to topoisomerase inhibitor drugs. In: British Journal of Cancer. 2002 ; Vol. 86, No. 9. pp. 1501-1509.
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