Comparative analysis of cell death induction by Taurolidine in different malignant human cancer cell lines

Five different malignant cell lines (HT29/Colon, Chang Liver/Liver, HT1080/fibrosarcoma, AsPC-1/pancreas and BxPC-3/pancreas) were incubated with increasing concentrations of TRD (100 μM, 250 μM and 1000 μM) for 6 h and 24 h. Cell viability, apoptosis and necrosis were analyzed by FACS analysis (Propidiumiodide/AnnexinV staining). Additionally, cells were co-incubated with the caspase Inhibitor z-VAD, the radical scavenger N-Acetylcystein (NAC) and the Gluthation depleting agent BSO to examine the contribution of caspase activation and reactive oxygen species in TRD induced cell death.All cell lines were susceptible to TRD induced cell death without resistance toward this anti-neoplastic agent. However, the dose response effects were varying largely between different cell lines. The effect of NAC and BSO co-treatment were highly different among cell lines - suggesting a cell line specific involvement of ROS in TRD induced cell death. Furthermore, impact of z-VAD mediated inhibition of caspases was differing strongly among the cell lines.This is the first study providing a simultaneous evaluation of the anti-neoplastic action of TRD across several malignant cell lines. The involvement of ROS and caspase activation was highly variable among the five cell lines, although all were susceptible to TRD induced cell death. Our results indicate, that TRD is likely to provide multifaceted cell death mechanisms leading to a cell line specific diversity.Taurolidine (TRD), a substance derived from the aminosulfoacid Taurin, was originally used in peritonitis and catheter related blood stream infections due to its anti-microbial and anti-inflammatory properties [1-3]. Over the last years, TRD has also been shown to exert anti-neoplastic activity in vitro as well as in vivo [4]. TRD induces cell death in a variety of malignant cell lines derived from colon carcinoma [5,6], squamous cell esophageal carcinoma [7] glioblastoma [8,9], melanoma [10,11], mesothelioma [12,13] and sarcoma