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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 |
| Affiliation: | 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 |