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An Organoruthenium Anticancer Agent Shows Unexpected Target Selectivity For Plectin |
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| Authors: | Dr Samuel M Meier M Sc Dominique Kreutz Dr Lilli Winter M Sc Matthias H M Klose M Sc Klaudia Cseh M Sc Tamara Weiss Dr Andrea Bileck M Sc Beatrix Alte Dr Johanna C Mader M Sc Samir Jana Dr Annesha Chatterjee Dr Arindam Bhattacharyya Michaela Hejl Dr Michael A Jakupec Priv-Doz Dr Petra Heffeter Prof Dr Walter Berger Prof Dr Christian G Hartinger Prof Dr Bernhard K Keppler Prof Dr Gerhard Wiche Prof Dr Christopher Gerner |
| Institution: | 1. Institut für Analytische Chemie, Universität Wien, Währinger Strasse 38, 1090 Wien, Austria;2. Department of Biochemistry and Cell Biology MFPL, Universität Wien, Dr.-Bohr-Gasse 9, 1030 Vienna, Austria;3. Forschungsplattform “Translational Cancer Therapy Research”, Universität Wien und Medizinische Universität Wien, Austria
Institut für Anorganische Chemie, Universität Wien, Austria;4. Institut für Anorganische Chemie, Universität Wien, Austria;5. St. Anna Kinderkrebsforschung, Vienna, Austria;6. Institut für Krebsforschung, Medizinische Universität Wien, Austria;7. Department für Zoology, University of Calcutta, 35 Ballygunge Circular Road, India;8. Forschungsplattform “Translational Cancer Therapy Research”, Universität Wien und Medizinische Universität Wien, Austria;9. School of Chemical Science, University of Auckland, New Zealand |
| Abstract: | Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock-out model in vitro. Plectin targeting shows potential as a strategy to inhibit tumor invasiveness as shown in cultured tumor spheroids while oral administration of plecstatin-1 to mice reduces tumor growth more efficiently in the invasive B16 melanoma than in the CT26 colon tumor model. |
| Keywords: | anticancer agents plectin proteomics ruthenium target identification |