gms | German Medical Science

Introduction: Taurolidine is a substance with anti-neoplastic activity against many tumor cells. Since the molecular mechanism of Taurolidine is still unknown, we sought to analyze the anti-neoplastic capacity of Taurultam (TRLT), a main metabolite of Taurolidine, in malignant human cell lines derived from pancreatic cancer (AsPC-1, BxPC-3, HPAF II, MiaPaca-2, Panc-1) and colon cancer (SW-480, HT-29 and HCT-116) in vitro. Additionally, involvement of caspase- and ROS- (reactive oxygen species) signaling in TRLT induced cell death was determined.

Material and methods: All cancer cell lines were incubated with Taurultam in increasing concentrations (100, 200, 500, 1000, 1500 and 2000 µmol/l) for 6 h, 12 h, 24 h and 48 h. The anti-neoplastic activity of TRLT was quantified by MTT-assay (cytotoxicity), BrdU-assay (inhibition of proliferation) and flowcytometric FACS-analysis with propidiumiodide and Annexin V (apoptosis induction).

Furthermore, growth curves were rendered using a real-time cell analyzer. In addition, co-incubation studies with z-VAD, an inhibitor of caspases, and NAC (N-acetylcystein), an inhibitor of ROS, were performed.

Results: In MTT-, BrdU- and real-time cell analyzer-assays, TRLT revealed a significant cytotoxic and anti-proliferative effect on all pancreatic and colon cancer cell-lines starting with concentrations of 500 µmol/l with a maximum effect at 1500 µmol/l. FACS analysis was characterized by a significant and strong apoptotic response upon stimulation by TRLT. Co-incubation with z-VAD/NAC indicated that both caspase- and ROS-signaling pathways are involved in cell death induction by TRLT.

Conclusion: It could be demonstrated for the first time, that TRLT provides anti-neoplastic effects in pancreatic and colon cancer cell lines - operating with different mechanisms e.g. inhibition of proliferation, direct cell toxicity and induction of apoptosis. Since both caspase- and ROS- signaling are involved, cell death induction by TRLT might be multilayered and - at least in part - responsible for the anti-neoplastic capacity of Taurolidine.