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Open Access Highly Accessed Research article

Gene expression analysis of cell death induction by Taurolidine in different malignant cell lines

Ansgar M Chromik1*, Stephan A Hahn2, Adrien Daigeler3, Annegret Flier1, Daniel Bulut4, Christina May1, Kamran Harati1, Jan Roschinsky1, Dominique Sülberg1, Dirk Weyhe1, Ulrich Mittelkötter1 and Waldemar Uhl1

Author Affiliations

1 Department of Visceral and General Surgery, St. Josef Hospital, Ruhr-University Bochum, Gudrunstrasse 56, D-44791 Bochum, Germany

2 Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Universitätsstraße 150, D-44780 Bochum, Germany

3 Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG-Unfallkrankenhaus, Ludwigshafen, Ludwig-Guttmann-Straße 13, D-67071 Ludwigshafen, Germany

4 Department of Medicine I, St. Josef Hospital, Ruhr-University Bochum, Gudrunstrasse 56, D-44791 Bochum, Germany

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BMC Cancer 2010, 10:595  doi:10.1186/1471-2407-10-595

Published: 30 October 2010

Abstract

Background

The anti-infective agent Taurolidine (TRD) has been shown to have cell death inducing properties, but the mechanism of its action is largely unknown. The aim of this study was to identify potential common target genes modulated at the transcriptional level following TRD treatment in tumour cell lines originating from different cancer types.

Methods

Five different malignant cell lines (HT29, Chang Liver, HT1080, AsPC-1 and BxPC-3) were incubated with TRD (100 μM, 250 μM and 1000 μM). Proliferation after 8 h and cell viability after 24 h were analyzed by BrdU assay and FACS analysis, respectively. Gene expression analyses were carried out using the Agilent -microarray platform to indentify genes which displayed conjoint regulation following the addition of TRD in all cell lines. Candidate genes were subjected to Ingenuity Pathways Analysis and selected genes were validated by qRT-PCR and Western Blot.

Results

TRD 250 μM caused a significant inhibition of proliferation as well as apoptotic cell death in all cell lines. Among cell death associated genes with the strongest regulation in gene expression, we identified pro-apoptotic transcription factors (EGR1, ATF3) as well as genes involved in the ER stress response (PPP1R15A), in ubiquitination (TRAF6) and mitochondrial apoptotic pathways (PMAIP1).

Conclusions

This is the first conjoint analysis of potential target genes of TRD which was performed simultaneously in different malignant cell lines. The results indicate that TRD might be involved in different signal transduction pathways leading to apoptosis.