Respiratory status determines the effect of emodin on cell viability
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Verónica I. Dumit1,2,3,4, Ralf M. Zerbes5,6, Stephanie Kaeser-Pebernard10, Michal Rackiewicz2,3,10, Mona T. Wall1,2, Christine Gretzmeier2,3, Victoria Küttner2,3, Martin van der Laan5,7,8, Ralf J. Braun9 and Jörn Dengjel1,2,3,7,10
1Freiburg Institute for Advanced Studies FRIAS, University of Freiburg, Freiburg, Germany
2Center for Biological Systems Analysis ZBSA, Freiburg, Germany
3Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany
4Core Facility Proteomics, ZBSA, University of Freiburg, Freiburg, Germany
5Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany
6Faculty of Biology, University of Freiburg, Freiburg, Germany
7BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany
8Medical Biochemistry and Molecular Biology, Center for Molecular Signaling, PZMS, Saarland University, Homburg, Germany
9Institute of Cell Biology, University of Bayreuth, Bayreuth, Germany
10Department of Biology, University of Fribourg, Fribourg, Switzerland
Jörn Dengjel, email: [email protected]
Verónica I. Dumit, email: [email protected]
Keywords: chemoproteomics, reactive oxygen species, mitochondria, anthraquinone, complex I
Received: September 09, 2016 Accepted: March 01, 2017 Published: March 21, 2017
The anthraquinone emodin has been shown to have antineoplastic properties and a wealth of unconnected effects have been linked to its use, most of which are likely secondary outcomes of the drug treatment. The primary activity of emodin on cells has remained unknown. In the present study we demonstrate dramatic and extensive effects of emodin on the redox state of cells and on mitochondrial homeostasis, irrespectively of the cell type and organism, ranging from the yeast Saccharomyces cerevisiae to human cell lines and primary cells. Emodin binds to redox-active enzymes and its effectiveness depends on the oxidative and respiratory status of cells. We show that cells with efficient respiratory metabolism are less susceptible to emodin, whereas cells under glycolytic metabolism are more vulnerable to the compound. Our findings indicate that emodin acts in a similar way as known uncouplers of the mitochondrial electron transport chain and causes oxidative stress that particularly disturbs cancer cells.
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