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| Description
| - Alfa-tokoferyl sukcinát je selektivní induktor apoptózy nádorových buněk. Alfa-tokoferyl sukcinát (alfa-TOS) je selektivní induktor apoptózy nádorových buněk, což zahrnuje akumulaci kyslíkových radikálů (ROS). Ukazujeme, že alfa-TOS inhibuje aktivitu SDH komplexu II (CII) interakcí s proximálním Q(P) a distálním Q(D) vazným místem pro ubichinon (UbQ). Buňky nesoucí mutaci na genu pro komplex II, nejsou citlivé na alfa -TOS a neprodukují ROS. Zavedení funkčního CII do těchto buněk, jim způsobilo citlivost na alfa -TOS. Navrhujeme, že alfa -TOS vytěsňuje UbQ z CII a způsobuje tvorbu kyslíkových radikálů. Naše data poukazují na CII jako na nový cíl v protinádorové terapii. (cs)
- Alpha-tocopheryl succinate is a selective inducer of apoptosis in cancer cells. The molecular target of alpha-TOS has not been identified. Here, we show that alpha-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ)-binding site (Q(P) and Q(D), respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of alpha-TOS compared to that of UbQ for the Q(P) and Q(D) sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and underwent apoptosis in the presence of alpha-TOS. Reconstitution of functional CII rendered CybL-mutant cells susceptible to alpha-TOS. We propose that alpha-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy.
- Alpha-tocopheryl succinate is a selective inducer of apoptosis in cancer cells. The molecular target of alpha-TOS has not been identified. Here, we show that alpha-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ)-binding site (Q(P) and Q(D), respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of alpha-TOS compared to that of UbQ for the Q(P) and Q(D) sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and underwent apoptosis in the presence of alpha-TOS. Reconstitution of functional CII rendered CybL-mutant cells susceptible to alpha-TOS. We propose that alpha-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy. (en)
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| Title
| - Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II
- Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II (en)
- Alfa-tokoferyl sukcinát indukuje apoptózu interakcí s mitochondriálním repiračním komplexem II v oblasti vazných míst pro ubichinon (cs)
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| skos:prefLabel
| - Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II
- Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II (en)
- Alfa-tokoferyl sukcinát indukuje apoptózu interakcí s mitochondriálním repiračním komplexem II v oblasti vazných míst pro ubichinon (cs)
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| skos:notation
| - RIV/00027162:_____/08:#0000328!RIV09-MZE-00027162
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| http://linked.open...avai/riv/aktivita
| |
| http://linked.open...avai/riv/aktivity
| - P(IAA500520702), P(KAN200520703), Z(AV0Z50520701), Z(MZE0002716201)
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/00027162:_____/08:#0000328
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| http://linked.open...riv/jazykVysledku
| |
| http://linked.open.../riv/klicovaSlova
| - alpha-tocopheryl succinate; complex II; ubiquinonebinding sites; reactive oxygen species; apoptosis; anti-cancer drug target (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
| - GB - Spojené království Velké Británie a Severního Irska
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
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| http://linked.open...in/vavai/riv/obor
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| http://linked.open...ichTvurcuVysledku
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| http://linked.open...cetTvurcuVysledku
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| http://linked.open...vavai/riv/projekt
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| http://linked.open...UplatneniVysledku
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| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Dong, L.
- Procházka, Lubomír
- Turánek, Jaroslav
- Freeman, R.
- Wang, X.
- Liu, J.
- Neužil, J.
- Valis, K.
- Dyason, J.
- Löw, P.
- Ralph, S.
- Scheffler, X.
- Swettenham, E.
- Witting, P.
- Zobalová, R.
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| http://linked.open...ain/vavai/riv/wos
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| http://linked.open...n/vavai/riv/zamer
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| issn
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| number of pages
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| is http://linked.open...avai/riv/vysledek
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