Mesalazine downregulates c-Myc in human colon cancer cells. A key to its chemopreventive action?

Aliment Pharmacol Ther. 2007 Jun 15;25(12):1443-9. doi: 10.1111/j.1365-2036.2007.03336.x.

Abstract

Background: Dysplasia and malignant transformation of colonocytes in ulcerative colitis are associated with overexpression of c-Myc and genes regulating cell survival. 5-Aminosalicylates such as mesalazine may reduce the development of colorectal cancer in ulcerative colitis, but the mechanisms of its chemopreventive action are not clear.

Aims: To examine whether mesalazine affects the expression of c-Myc in human colon cancer cell lines.

Methods: Human colon cancer cells were treated with vehicle or mesalazine (4 mm or 40 mm). We examined: (i) mRNA expression by gene array, (ii) protein expression by Western blotting and immunohistochemistry and (iii) apoptosis by Annexin V labelling.

Results: Mesalazine significantly reduced expression of c-Myc mRNA and protein.

Conclusions: Mesalazine downregulates gene and protein expression of c-Myc. The apoptotic and growth inhibitory effects of mesalazine are dose-dependent. Expression of c-Myc is significantly reduced by mesalazine 40 mm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Apoptosis / drug effects
  • Blotting, Western / methods
  • Colitis, Ulcerative / drug therapy
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / prevention & control*
  • Down-Regulation*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression / drug effects
  • Humans
  • Immunohistochemistry / methods
  • Mesalamine / pharmacology*
  • Mesalamine / therapeutic use
  • Proto-Oncogene Proteins c-myc / metabolism
  • Treatment Outcome

Substances

  • Annexin A5
  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-myc
  • Mesalamine