Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anti-cancer activity via mitochondrial complex

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F11%3A00361293" target="_blank" >RIV/61388963:_____/11:00361293 - isvavai.cz</a>
Alternative codes found
RIV/86652036:_____/11:00361293
Result on the web
<a href="http://dx.doi.org/10.1016/j.freeradbiomed.2011.02.032" target="_blank" >http://dx.doi.org/10.1016/j.freeradbiomed.2011.02.032</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.freeradbiomed.2011.02.032" target="_blank" >10.1016/j.freeradbiomed.2011.02.032</a>

Result language
angličtina
Original language name
Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anti-cancer activity via mitochondrial complex
Original language description
Mitochondrially targeted vitamin E succinate (MitoVES) has enhanced pro-apoptotic and anti-cancer activities. It caused apoptosis and generation of ROS in CII-proficient malignant cells but not their CII-dysfunctional counterparts. It inhibited SDH activity of CII with IC50 of 80 mu M and electron transfer from CII to CIII with IC50 of 1.5 mu M. Molecular modeling predicted its succinyl group anchored into the proximal CII ubiquinone (UbQ)-binding site and reduced interaction energies for its serially shorter phytyl chain homologs correlated with their lower effects on apoptosis induction, ROS generation, and SDH activity. Mutation of the UbQ-binding Ser(68) within the proximal site of the CII SDHC subunit suppressed both ROS generation and apoptosis induction by it. We propose that mitochondrial targeting of VES with an 11-carbon chain localizes the agent into an ideal position across the interface of the mitochondrial inner membrane and matrix, optimizing its anti-cancer effect
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
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Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Publication year
2011
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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