Mesalamine inhibits epithelial beta-catenin activation in chronic ulcerative colitis

Gastroenterology. 2010 Feb;138(2):595-605, 605.e1-3. doi: 10.1053/j.gastro.2009.10.038. Epub 2009 Oct 29.


Background & aims: Mesalamine is a mainstay therapeutic agent in chronic ulcerative colitis (CUC) in which condition it reverses crypt architectural changes and reduces colitis-associated cancer (CAC). The present study addressed the possibility that mesalamine reduces beta-catenin-associated progenitor cell activation, Akt-phosphorylated beta-catenin(Ser552) (P-beta-catenin), and colitis-induced dysplasia (CID).

Methods: Effects of mesalamine on P-beta-catenin staining and function were assessed by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in biopsy specimens of CUC in mild or "refractory" severe mucosal inflammation. Effects of mesalamine on epithelial proliferation and activation of Akt and beta-catenin were assessed in interleukin (IL)-10(-/-) colitis and CID by immunohistochemistry and Western blotting. Dysplasia was assessed by counting the number and lengths of lesions per colon.

Results: Data from IL-10(-/-) and human colitis samples show that mesalamine reduced Akt activation and P-beta-catenin levels in the middle and upper crypt. Reductions in P-beta-catenin in CUC biopsy specimens with severe inflammation suggested that mesalamine reduced P-beta-catenin levels in tissue refractory to mesalamine's anti-inflammatory effects. In IL-10(-/-) mice, mesalamine reduced CID concordant with inhibition of crypt Akt and beta-catenin signaling.

Conclusions: The results are consistent with the model that mesalamine contributes to chemoprevention in CAC by reducing beta-catenin signaling within intestinal progenitors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Biopsy
  • Cell Proliferation / drug effects
  • Colitis, Ulcerative / metabolism*
  • Colitis, Ulcerative / pathology
  • Colon / drug effects
  • Colon / metabolism*
  • Colon / pathology
  • Disease Models, Animal
  • Disease Progression
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Mesalamine / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • beta Catenin / metabolism*


  • Anti-Inflammatory Agents, Non-Steroidal
  • beta Catenin
  • Interleukin-10
  • Mesalamine