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The tumor‐suppressive reagent taurolidine is an inhibitor of protein biosynthesis
Author(s) -
Braumann Chris,
Henke Wolfgang,
Jacobi Christoph A.,
Dubiel Wolfgang
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20393
Subject(s) - transcription preinitiation complex , protein biosynthesis , translation (biology) , messenger rna , transcription (linguistics) , cancer research , protein synthesis inhibitor , microbiology and biotechnology , chemistry , biology , gene expression , biochemistry , gene , promoter , linguistics , philosophy , cycloheximide
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 IκBα, 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 IC 50 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. © 2004 Wiley‐Liss, Inc.