The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human Cells
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 c...
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2014-09-01
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doaj-4ed61d1af0234c64b9c3db55e9c59ce02020-11-25T00:34:32ZengMDPI AGMolecules1420-30492014-09-01199150881510210.3390/molecules190915088molecules190915088The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human CellsPieter Spincemaille0Hamed Alborzinia1Jeroen Dekervel2Petra Windmolders3Jos van Pelt4David Cassiman5Olivier Cheneval6David J. Craik7Julia Schur8Ingo Ott9Stefan Wölfl10Bruno P. A. Cammue11Karin Thevissen12Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, Heverlee 3001, BelgiumInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, Heidelberg 69120, GermanyDepartment of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, Leuven 3000, BelgiumDepartment of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, Leuven 3000, BelgiumDepartment of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, Leuven 3000, BelgiumDepartment of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, Leuven 3000, BelgiumDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Old 4072, AustraliaDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Old 4072, AustraliaInstitute of Medicinal and Pharmaceutical Chemistry, Technische Universität, Braunschweig, Beethovenstrasse 55, Braunschweig 38106, GermanyInstitute of Medicinal and Pharmaceutical Chemistry, Technische Universität, Braunschweig, Beethovenstrasse 55, Braunschweig 38106, GermanyInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, Heidelberg 69120, GermanyCentre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, Heverlee 3001, BelgiumCentre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, Heverlee 3001, BelgiumWe 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.http://www.mdpi.com/1420-3049/19/9/15088cisplatinOSIP108glycolysisrespirationreal-time online monitoring |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pieter Spincemaille Hamed Alborzinia Jeroen Dekervel Petra Windmolders Jos van Pelt David Cassiman Olivier Cheneval David J. Craik Julia Schur Ingo Ott Stefan Wölfl Bruno P. A. Cammue Karin Thevissen |
spellingShingle |
Pieter Spincemaille Hamed Alborzinia Jeroen Dekervel Petra Windmolders Jos van Pelt David Cassiman Olivier Cheneval David J. Craik Julia Schur Ingo Ott Stefan Wölfl Bruno P. A. Cammue Karin Thevissen The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human Cells Molecules cisplatin OSIP108 glycolysis respiration real-time online monitoring |
author_facet |
Pieter Spincemaille Hamed Alborzinia Jeroen Dekervel Petra Windmolders Jos van Pelt David Cassiman Olivier Cheneval David J. Craik Julia Schur Ingo Ott Stefan Wölfl Bruno P. A. Cammue Karin Thevissen |
author_sort |
Pieter Spincemaille |
title |
The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human Cells |
title_short |
The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human Cells |
title_full |
The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human Cells |
title_fullStr |
The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human Cells |
title_full_unstemmed |
The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human Cells |
title_sort |
plant decapeptide osip108 can alleviate mitochondrial dysfunction induced by cisplatin in human cells |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2014-09-01 |
description |
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. |
topic |
cisplatin OSIP108 glycolysis respiration real-time online monitoring |
url |
http://www.mdpi.com/1420-3049/19/9/15088 |
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