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

Biochem Pharmacol. 2008 Feb 1;75(3):668-76. doi: 10.1016/j.bcp.2007.09.020. Epub 2007 Sep 29.


The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway may have a pathogenic role in colorectal cancer (CRC). Recent studies suggest that 5-aminosalicylic 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-alpha or IL-1beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / pathology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / physiology*
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Dinoprostone / biosynthesis
  • Dose-Response Relationship, Drug
  • Humans
  • Interleukin-1beta / pharmacology
  • Mesalamine / pharmacology*
  • Transforming Growth Factor alpha / pharmacology


  • Cyclooxygenase 2 Inhibitors
  • Interleukin-1beta
  • Transforming Growth Factor alpha
  • Mesalamine
  • Cyclooxygenase 2
  • Dinoprostone