Document Detail


Mesalazine inhibits the beta-catenin signalling pathway acting through the upregulation of mu-protocadherin gene in colo-rectal cancer cells.
MedLine Citation:
PMID:  19785626     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 beta-catenin signalling could induce these cellular effects. AIM: To characterize better the capacity of 5-ASA to inhibit the beta-catenin signalling pathway. METHODS: 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. RESULTS: 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. CONCLUSION: These findings suggest that mu-protocadherin might be employed as a biological marker to monitor the chemopreventive efficacy of 5-ASA.
Authors:
S Parenti; F Ferrarini; R Zini; M Montanari; L Losi; B Canovi; S Ferrari; A Grande
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Alimentary pharmacology & therapeutics     Volume:  31     ISSN:  1365-2036     ISO Abbreviation:  Aliment. Pharmacol. Ther.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-16     Completed Date:  2010-05-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8707234     Medline TA:  Aliment Pharmacol Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  108-19     Citation Subset:  IM    
Affiliation:
Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
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MeSH Terms
Descriptor/Qualifier:
Cadherins / genetics,  metabolism*
Cell Line, Tumor
Colorectal Neoplasms / drug therapy*,  genetics
Gene Expression Regulation, Neoplastic / drug effects
Humans
Mesalamine / pharmacology*
Signal Transduction / drug effects*,  genetics
Up-Regulation / drug effects
beta Catenin / antagonists & inhibitors*,  genetics
Chemical
Reg. No./Substance:
0/Cadherins; 0/beta Catenin; 89-57-6/Mesalamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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