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.

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The interaction and the consecutive down regulation of TSPO by hemin played an important role in the control of Caco-2 cell viability. The presented data suggest that TSPO might contribute to protect cells from potential toxic compounds such as free tetrapyrroles, candidating this receptor as a survival receptor protein.

Mu-protocadherin (MUCDHL) is an adhesion molecule predominantly expressed by colorectal epithelial cells which is markedly downregulated upon malignant transformation. Notably, treatment of colorectal cancer (CRC) cells with mesalazine lead to increased expression of MUCDHL, and is associated with sequestration of β-catenin on the plasma membrane and inhibition of its transcriptional activity. To better characterize the causal relationship between β-catenin and MUCDHL expression, we performed various experiments in which CRC cell lines and normal colonic organoids were subjected to culture conditions inhibiting (FH535 treatment, transcription factor 7-like 2 siRNA inactivation, Wnt withdrawal) or stimulating (LiCl treatment) β-catenin activity. We show here that expression of MUCDHL is negatively regulated by functional activation of the β-catenin signaling pathway. This finding was observed in cell culture systems representing conditions of physiological stimulation and upon constitutive activation of β-catenin in CRC. The ability of MUCDHL to sequester and inhibit β-catenin appears to provide a positive feedback enforcing the effect of β-catenin inhibitors rather than serving as the primary mechanism responsible for β-catenin inhibition. Moreover, MUCDHL might have a role as biomarker in the development of CRC chemoprevention drugs endowed with β-catenin inhibitory activity.