Cyclooxygenase-2-dependent and -independent inhibition of proliferation of colon cancer cells by 5-aminosalicylic acid

Carmine Stolfi, Daniele Fina, Roberta Caruso, Flavio Caprioli, Massimiliano Sarra, Massimo Claudio Fantini, Angelamaria Rizzo, Francesco Pallone, Giovanni Monteleone

Research output: Contribution to journalArticlepeer-review

Abstract

The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway may have a pathogenic role in colorectal cancer (CRC). Recent studies suggest that 5-aminosalycilic acid (5-ASA) reduces the risk of inflammatory bowel disease-related CRC, but the mechanism by which 5-ASA interferes with CRC cell growth remains unknown. In this study, we have examined whether the negative effect of 5-ASA on CRC cells is dependent on COX-2/PGE2 axis inhibition. We show that 5-ASA down-regulates both constitutive and TNF-α or IL-1β-induced COX-2 in HT-115 and HT-29 cells. Inhibition of COX-2 by 5-ASA occurs at the RNA and protein level, and is associated with a significant decrease in PGE2 synthesis, arrest of growth and enhanced death of CRC cells. However, exogenous PGE2 does not revert the 5-ASA-mediated CRC cell proliferation block. 5-ASA also inhibits the growth of DLD-1, a COX-deficient CRC cell line, thus suggesting that the anti-proliferative effect of 5-ASA on CRC cells is not strictly dependent on the inhibition of COX-2/PGE2. Taken together our data indicate that 5-ASA causes both a COX-2-dependent and -independent inhibition of CRC cell growth.

Original languageEnglish
Pages (from-to)668-676
Number of pages9
JournalBiochemical Pharmacology
Volume75
Issue number3
DOIs
Publication statusPublished - Feb 1 2008

Keywords

  • 5-ASA
  • Colon cancer
  • COX-2

ASJC Scopus subject areas

  • Pharmacology

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