Oral Administration of the Anti-proliferative Substance Taurolidine Has No Impact on Dextran Sulfate Sodium Induced Colitis-associated Carcinogenesis in Mice

Overview

Journal J Carcinog

Publisher Biomed Central

Date 2010 May 6

PMID 20442801

Authors

Ansgar Michael Chromik

Sebastian Huss

Hayssam Osseili

Adrien Daigeler

Sabine Kersting

Dominique Sulberg

Ulrich Mittelkotter

Thomas Herdegen

Waldemar Uhl

Annette M Muller

Affiliations

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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 (beta-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, beta-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.

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