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Molecules 2014, 19(9), 15088-15102; doi:10.3390/molecules190915088

The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human Cells

1
Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, Heverlee 3001, Belgium
2
Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, Heidelberg 69120, Germany
3
Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, Leuven 3000, Belgium
4
Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Old 4072, Australia
5
Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität, Braunschweig, Beethovenstrasse 55, Braunschweig 38106, Germany
6
Department of Plant Systems Biology, VIB, Technologiepark 927, Ghent 9052, Belgium
*
Author to whom correspondence should be addressed.
Received: 11 July 2014 / Revised: 10 September 2014 / Accepted: 11 September 2014 / Published: 19 September 2014
(This article belongs to the Special Issue Peptide Chemistry)
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Abstract

We investigated the effect of the Arabidopsis thaliana-derived decapeptide OSIP108 on human cell tolerance to the chemotherapeutic agent cisplatin (Cp), which induces apoptosis and mitochondrial dysfunction. We found that OSIP108 increases the tolerance of HepG2 cells to Cp and prevents Cp-induced changes in basic cellular metabolism. More specifically, we demonstrate that OSIP108 reduces Cp-induced inhibition of respiration, decreases glycolysis and prevents Cp-uptake in HepG2 cells. Apart from its protective action against Cp in human cells, OSIP108 also increases the yeast Saccharomyces cerevisiae tolerance to Cp. A limited yeast-based study of OSIP108 analogs showed that cyclization does not severely affect its activity, which was further confirmed in HepG2 cells. Furthermore, the similarity in the activity of the D-stereoisomer (mirror image) form of OSIP108 with the L-stereoisomer suggests that its mode of action does not involve binding to a stereospecific receptor. In addition, as OSIP108 decreases Cp uptake in HepG2 cells and the anti-Cp activity of OSIP108 analogs without free cysteine is reduced, OSIP108 seems to protect against Cp-induced toxicity only partly via complexation. Taken together, our data indicate that OSIP108 and its cyclic derivatives can protect against Cp-induced toxicity and, thus, show potential as treatment options for mitochondrial dysfunction- and apoptosis-related conditions. View Full-Text
Keywords: cisplatin; OSIP108; glycolysis; respiration; real-time online monitoring cisplatin; OSIP108; glycolysis; respiration; real-time online monitoring
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MDPI and ACS Style

Spincemaille, P.; Alborzinia, H.; Dekervel, J.; Windmolders, P.; van Pelt, J.; Cassiman, D.; Cheneval, O.; Craik, D.J.; Schur, J.; Ott, I.; Wölfl, S.; Cammue, B.P.A.; Thevissen, K. The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human Cells. Molecules 2014, 19, 15088-15102.

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