Comparative analysis of cell death induction by Taurolidine in different malignant human cancer cell lines.
BACKGROUND
Taurolidine (TRD) represents an anti-infective substance with anti-neoplastic activity in many malignant cell lines. So far, the knowledge about the cell death inducing mechanisms and pathways activated by TRD is limited. The aim of this study was therefore, to perform a comparative analysis of cell death induction by TRD simultaneously in different malignant cell lines.


METHODS
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 microM, 250 microM and 1000 microM) 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.


RESULTS
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.


CONCLUSIONS
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.
Chromik
Ansgar M
AM
Department of Visceral and General Surgery, St Josef Hospital, Ruhr-University Bochum, Germany. a.chromik@klinikum-bochum.de
Daigeler
Adrien
A
Bulut
Daniel
D
Flier
Annegret
A
May
Christina
C
Harati
Kamran
K
Roschinsky
Jan
J
Sülberg
Dominique
D
Ritter
Peter R
PR
Mittelkötter
Ulrich
U
Hahn
Stephan A
SA
Uhl
Waldemar
W
D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000037:antagonists & inhibitors; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D017382:Reactive Oxygen Species; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013829:Thiadiazines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D013829:Thiadiazines; D013654:Taurine; C012566:taurolidine; D020169:Caspases; D005978:Glutathione; D000111:Acetylcysteine