The tumor-suppressive reagent taurolidine is an inhibitor of protein biosynthesis.
Taurolidine has been successfully used as a disinfectant and to prevent the spreading and growth of tumor cells after surgical excision. However, the underlying mechanisms regarding its effects remain obscure. Here, we show that taurolidine treatment reduces endogenous levels of IkappaBalpha, p105, c-Jun, p53 and p27 in a dose-dependent manner in colon adenocarcinoma cells, which can be in part due to massive cell death. Because expression of tested proteins was affected by taurolidine, its influence on protein expression was studied. In the coupled transcription/translation system, taurolidine inhibited c-Jun expression with an IC50 value of 1.4 mM. There was no or little effect on transcription. In contrast, translation of c-Jun or p53 mRNA was completely inhibited by taurolidine. To determine which step of translation was affected, prominent complexes occurring in the course of translation were analyzed by density gradient centrifugation. In the presence of taurolidine, no preinitiation translation complex was assembled. Taurolidine also suppressed protein expression in bacteria. Based on our data, we conclude that taurolidine blocks a fundamental early phase of translation, which might explain its effects as a disinfectant and inhibitor of tumor growth.
Braumann
Chris
C
Department of General, Visceral, Vascular and Thoracic Surgery, Charité, Universitätsmedizin Berlin, Berlin, Germany.
Henke
Wolfgang
W
Jacobi
Christoph A
CA
Dubiel
Wolfgang
W
D000230:Adenocarcinoma / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001419:Bacteria; D003110:Colonic Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D014176:Protein Biosynthesis / Q000187:drug effects*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013829:Thiadiazines / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D013829:Thiadiazines; D014157:Transcription Factors; D013654:Taurine; C012566:taurolidine