title: Taurolidine induces epithelial-mesenchymal transition via up-regulation of the transcription factor Snail in human pancreatic cancer cell lines.
abstract: OBJECTIVE
  The taurine derivative taurolidine (TRD) exerts anti-neoplastic effects in a variety of tumor models. On the other hand, TRD at low doses was shown to reduce cell-cell adhesion, a prerequisite for metastasis. The aim of this study was to elucidate the effects of low-dose TRD on pancreatic cancer.
  
  
  METHODS
  Human pancreatic cancer cell lines representing diverse states of differentiation were exposed to TRD for 24 h. Cell viability was assessed by MTT assay and trypan blue staining, apoptosis by caspase-3/7 activity, and flow-cytometric cell cycle analysis. Expression of Snail and E-cadherin was analyzed by polymerase chain reaction and Western blotting.
  
  
  RESULTS
  MTT-tested viability of all pancreatic cancer cell lines decreased dose-dependently up to 50 % of the untreated control. In contrast to staurosporine TRD (100 and 250 μM) did not induce apoptosis but increased the percentage of cells in G1/G0 arrest. Correlation of MTT test and trypan blue staining revealed a decreased adherence of vital tumor cells at 250 μM TRD. This was associated with reduced expression of the adhesion molecule E-cadherin and an increased expression of the transcription factor Snail, a regulator of epithelial-mesenchymal transition (EMT).
  
  
  CONCLUSIONS
  Low-dose TRD reduces not only viability but also cell-cell adherence and E-cadherin expression of pancreatic cancer cells, whereas the expression of the EMT inducer Snail was increased. By induction of these EMT hallmarks, low-dose TRD may promote metastasis in pancreatic cancer.
authors.affiliation: Department of Surgery I, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Hotz
authors.forename: Ulrike
authors.initials: U
authors.lastname: Erben
authors.forename: Marco
authors.initials: M
authors.lastname: Arndt
authors.forename: Heinz J
authors.initials: HJ
authors.lastname: Buhr
authors.forename: Hubert G
authors.initials: HG
authors.lastname: Hotz
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013829:Thiadiazines / Q000008:administration & dosage / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D000071250:Snail Family Transcription Factors; D013829:Thiadiazines; D014157:Transcription Factors; D013654:Taurine; C012566:taurolidine