Single Versus Double Ring Structure: Search for Best Anti-Neoplastic Driver in Colon and Pancreatic Cancer Cells-Taurultam or Taurolidine?
Background: Since the molecular mechanism of the well-known anti-infective and antineoplastic substance Taurolidine (TRD) is still unknown, we sought to analyze the anti-neoplastic capacity of its main metabolite Taurultam (TAU) 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.
Methods: Cell lines were incubated with TAU or TRD in increasing concentrations for 24h and 48h. Comprehensive analyses were performed to quantify the anti-neoplastic activity of TAU: Analysis of cytotoxicity via MTT-assay, inhibition of proliferation via BrdU and induction of apoptosis and necrosis via FACS-analysis. Furthermore, cell growth was monitored using a real-time cell analyzer.
Results: TAU revealed a significant cytotoxic and anti-proliferative effect on all pancreatic and colon cancer cell-lines as well in MTT- and BrdU- assays as in the real-time cell analyzer. Furthermore, FACS analyses were characterized by a significant apoptotic and necrotic response upon stimulation with TAU. In contrast to TRD antineoplastic effects were noticeable lower.
Conclusion: It could be demonstrated for the first time, that TAU provides antineoplastic effects operating through mechanisms like its parent compound TRD. However, our results show clearly that TAU is not the only anti-neoplastic active metabolite of TRD. Hence, our data suggest that the efficiency of TRD against cancer cells is rather based on the methylol-containing species released during hydrolysis. These promising results are the first step towards the development of a novel substance combining the high anti-neoplastic capacity of TRD with better molecular properties of TAU, like a higher solubility in aqueous solution.