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


OBJECTIVE
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.


CONCLUSIONS
These findings suggest that mu-protocadherin might be employed as a biological marker to monitor the chemopreventive efficacy of 5-ASA.
Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
S
S
Parenti
F
F
Ferrarini
R
R
Zini
M
M
Montanari
L
L
Losi
B
B
Canovi
S
S
Ferrari
A
A
Grande
D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019804:Mesalamine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000235:genetics
D015820:Cadherins; D051176:beta Catenin; D019804:Mesalamine