Targeting succinate:ubiquinone reductase potentiates the efficacy of anticancer therapy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F16%3A00461853" target="_blank" >RIV/68081707:_____/16:00461853 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/16:00111637

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bbamcr.2016.04.026" target="_blank" >http://dx.doi.org/10.1016/j.bbamcr.2016.04.026</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbamcr.2016.04.026" target="_blank" >10.1016/j.bbamcr.2016.04.026</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Targeting succinate:ubiquinone reductase potentiates the efficacy of anticancer therapy

Popis výsledku v původním jazyce

Mitochondria play a pivotal role in apoptosis: permeabilization of the outer mitochondria! membrane and the release of pro-apoptotic proteins from the intermembrane space of mitochondria are regarded as the key event in apoptosis induction. Here we demonstrate how non-toxic doses of the mitochondrial Complex II inhibitor thenoyltrifluoroacetone (TTFA), which specifically inhibits the ubiquinone-binding site of succinate dehydrogenase (SDH), synergistically stimulated cell death, induced by harmless doses of cisplatin in a panel of chemoresistant neuroblastoma cell lines. Apoptotic cell death was confirmed by cytochrome c release from the mitochondria, cleavage of poly ADP-ribose polymerase, processing of caspase-3, which is an important executive enzyme in apoptosis, and caspase-3-like activity. Methyl malonate, an inhibitor of the SDHA subunit partially reversed apoptosis stimulated by TTFA in SK-N-BE(2) neuroblastoma cells (NB), indicating that sensitization requires oxidation of succinate.

Název v anglickém jazyce

Targeting succinate:ubiquinone reductase potentiates the efficacy of anticancer therapy

Popis výsledku anglicky

Mitochondria play a pivotal role in apoptosis: permeabilization of the outer mitochondria! membrane and the release of pro-apoptotic proteins from the intermembrane space of mitochondria are regarded as the key event in apoptosis induction. Here we demonstrate how non-toxic doses of the mitochondrial Complex II inhibitor thenoyltrifluoroacetone (TTFA), which specifically inhibits the ubiquinone-binding site of succinate dehydrogenase (SDH), synergistically stimulated cell death, induced by harmless doses of cisplatin in a panel of chemoresistant neuroblastoma cell lines. Apoptotic cell death was confirmed by cytochrome c release from the mitochondria, cleavage of poly ADP-ribose polymerase, processing of caspase-3, which is an important executive enzyme in apoptosis, and caspase-3-like activity. Methyl malonate, an inhibitor of the SDHA subunit partially reversed apoptosis stimulated by TTFA in SK-N-BE(2) neuroblastoma cells (NB), indicating that sensitization requires oxidation of succinate.

Druh

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

CEP obor

BO - Biofyzika

OECD FORD obor

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Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Biochimica Et Biophysica Acta-Molecular Cell Research

ISSN

0167-4889

e-ISSN

—

Svazek periodika

1863

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

7

Strana od-do

2065-2071

Kód UT WoS článku

000378671900012

EID výsledku v databázi Scopus

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