Oral administration of the anti-proliferative substance taurolidine has no impact on dextran sulfate sodium-induced colitis-associated carcinogenesis in mice

Posted by Article Type, Issue, Original Article, Vol 9,Issue 1Posted on

Ansgar Michael Chromik1, Sebastian Huss2, Hayssam Osseili1, Adrien Daigeler3, Sabine Kersting1, Dominique Sulberg1, Ulrich Mittelkotter1, Thomas Herdegen4, Waldemar Uhl1, Annette M Muller2
1Department of General and Visceral Surgery, St. Josef Hospital, Campus Kiel, Germany.
2Department of Pediatric Pathology, University of Bonn, Campus Kiel, Germany.
3Department of Plastic Surgery, University Hospital Bergmannsheil, Ruhr-University Bochum, Campus Kiel, Germany.
4Institute of Pharmacology, University Hospital of Schleswig-Holstein, Campus Kiel, Germany.
DOI:10.4103/1477-3163.62536

ABSTRACT

Background: New chemopreventive strategies for ulcerative colitis (UC)-associated dysplasia and cancer have to be evaluated. Taurolidine (TRD) has anti-inflammatory, anti-proliferative and anti-neoplastic properties with almost absent toxicity. The aim of the study was to determine whether TRD decreases dysplasia in the well-characterized Dextran Sulfate Sodium – Azoxymethane (DSS-AOM) animal model for UC-associated carcinogenesis. Material and Methods: The DSS-AOM model of carcinogenesis was induced in female inbred C57BL/6 mice. Half of the mice were treated with TRD, the other served as control. After 100 days macroscopic, histological and immunhistochemical (β-Catenin, E-Cadherin, SOX9, Ki-67, Cyclin-D1) examination of the colon was performed. Results: Incidence, multiplicity, grading and growth pattern of adenomas did not differ significantly between TRD and control group. In all animals, inflammatory changes were absent. Immunhistochemistry revealed increased expression of Ki-67, β-catenin, SOX9 and Cyclin-D1 in adenomas compared to normal mucosa – without significant difference between TRD and control treatment. Conclusion: Oral administration of TRD has no impact on DSS-induced colitis-associated carcinogenesis. However, SOX9 and Cyclin-D1 representing key members of the Wnt pathway have not yet been described in the DSS-AOM model of carcinogenesis – underlining the importance of this oncogenic pathway in this setting.

Keywords: Carcinogenesis, C57BL6 mice, Dextran Sulfate Sodium, experimental colitis, inflammatory bowel disease, Taurolidin, Taurolin, TRD.