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


OBJECTIVE
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.
Chu
E C
EC
Department of Medicine, Division of Gastroenterology, VA Long Beach Healthcare System, Long Beach, CA, USA. eric.chu2@med.va.gov
Chai
J
J
Ahluwalia
A
A
Tarnawski
A S
AS
D017304:Annexin A5 / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D003093:Colitis, Ulcerative / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019804:Mesalamine / Q000494:pharmacology* / Q000627:therapeutic use; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016896:Treatment Outcome
D017304:Annexin A5; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D019804:Mesalamine