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Mesalazine inhibits the β ‐catenin signalling pathway acting through the upregulation of μ‐protocadherin gene in colo‐rectal cancer cells
Author(s) -
PARENTI S.,
FERRARINI F.,
ZINI R.,
MONTANARI M.,
LOSI L.,
CANOVI B.,
FERRARI S.,
GRANDE A.
Publication year - 2010
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2009.04149.x
Subject(s) - colorectal cancer , catenin , downregulation and upregulation , medicine , cancer research , apoptosis , cell growth , cancer , pharmacology , signal transduction , gene , microbiology and biotechnology , biology , wnt signaling pathway , biochemistry
Summary Background 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 β‐catenin signalling could induce these cellular effects. Aim To characterize better the capacity of 5‐ASA to inhibit the β‐catenin signalling pathway. Methods Genes belonging to the β‐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. Results The results obtained indicated that 5‐ASA induces the expression of a protein called μ‐protocadherin that belongs to the cadherin superfamily and is able to sequester β‐catenin on the plasmatic membrane of treated cells hampering its function. Conclusion These findings suggest that μ‐protocadherin might be employed as a biological marker to monitor the chemopreventive efficacy of 5‐ASA.