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Mesalazine inhibits the beta-catenin signalling pathway acting through the upregulation of mu-protocadherin gene in colo-rectal cancer cells


, : Mesalazine inhibits the beta-catenin signalling pathway acting through the upregulation of mu-protocadherin gene in colo-rectal cancer cells. Alimentary Pharmacology & Therapeutics 31(1): 108-119

Several reports indicate that mesalazine (5-aminosalicylic acid, 5-ASA) is a promising candidate for the chemoprevention of colo-rectal cancer because of its ability to reach the purpose avoiding the unwanted side effects usually associated with prolonged administration of nonsteroidal anti-inflammatory drugs. This activity of 5-ASA is probably the consequence of a number of effects determined on colo-rectal cancer cells, consisting of reduced proliferation, increased apoptosis and activation of cell cycle checkpoints and DNA repair processes. A recent observation has suggested that inhibition of beta-catenin signalling could induce these cellular effects. To characterize better the capacity of 5-ASA to inhibit the beta-catenin signalling pathway. Genes belonging to the beta-catenin signalling pathway were analysed in colo-rectal cancer cell lines treated with 5-ASA using a combination of laboratory assays that are able to detect their phenotypic expression and functional activity. The results obtained indicated that 5-ASA induces the expression of a protein called mu-protocadherin that belongs to the cadherin superfamily and is able to sequester beta-catenin on the plasmatic membrane of treated cells hampering its function. These findings suggest that mu-protocadherin might be employed as a biological marker to monitor the chemopreventive efficacy of 5-ASA.

US$19.90

PMID: 19785626

DOI: 10.1111/j.1365-2036.2009.04149.x


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