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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/86652036:_____/11:00361293

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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

Název v anglickém jazyce

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

Popis výsledku anglicky

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

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2011

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

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Svazek periodika

286

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

3717-3728

Kód UT WoS článku

000286653200054

EID výsledku v databázi Scopus

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