Abstract
BackgroundThe 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.MethodsFive 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.ResultsTRD 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).ConclusionsThis 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.
Highlights
The anti-infective agent Taurolidine (TRD) has been shown to have cell death inducing properties, but the mechanism of its action is largely unknown
In all cell lines except HT29, even the lowest TRD concentration (100 μM) was capable of inhibiting proliferation leading to values of proliferating cells ranging between 53.4% (± 11.0%) (Chang Liver) and 93.8% (± 8.1%) (BxPC-3) which was significantly lower compared to untreated controls (100%) (Povidon 5%)
This study provides the first identification of potential common target genes modulated by TRD treatment of cell lines originating from four different cancer types
Summary
The anti-infective agent Taurolidine (TRD) has been shown to have cell death inducing properties, but the mechanism of its action is largely unknown. Taurolidine (TRD) - a derivate of the aminosulfoacid Taurin - has been clinically used for many years in peritonitis and catheter related blood stream infections due to its anti-microbial and anti-inflammatory properties [1,2,3]. It has been shown, that TRD exerts anti-proliferative and anti-neoplastic activity in vitro as well as in vivo [4,5]. The aim of this study was to analyse gene expression by microarray analyses simultaneously in different malignant cell lines - to identify potential TRD target genes which displayed conjoint regulation in all cell lines
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