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Description
| - We investigated whether alpha-TOS and several novel vitamin E analogs kill breast cancer cells overexpressing the antiapoptotic receptor protein HER2/erbB2. The agents induced apoptosis at comparable levels in both erbB2-low and -high cells. Generation of ROS preceded mitochondrial destabilization and execution of apoptosis. Dissipation of DeltaPsi(m) was followed by cytochrome c and Smac/Diablo re-localization and caspase-dependent cleavage of death substrate. A resistance to apoptosis for the corresponding rho(0) counterparts confirmed a critical dependency for mitochondria during the induction of apoptosis in breast cancer cells mediated by VE analogs and linked apoptosis to generation of radicals. alpha-TOS thus causes efficient apoptosis in breast cancer cells independent of their erbB2 status. Since erbB2 is frequently over-expressed in breast cancers and renders the neoplastic disease resistant to established treatment, our findings are of clinical interest.
- We investigated whether alpha-TOS and several novel vitamin E analogs kill breast cancer cells overexpressing the antiapoptotic receptor protein HER2/erbB2. The agents induced apoptosis at comparable levels in both erbB2-low and -high cells. Generation of ROS preceded mitochondrial destabilization and execution of apoptosis. Dissipation of DeltaPsi(m) was followed by cytochrome c and Smac/Diablo re-localization and caspase-dependent cleavage of death substrate. A resistance to apoptosis for the corresponding rho(0) counterparts confirmed a critical dependency for mitochondria during the induction of apoptosis in breast cancer cells mediated by VE analogs and linked apoptosis to generation of radicals. alpha-TOS thus causes efficient apoptosis in breast cancer cells independent of their erbB2 status. Since erbB2 is frequently over-expressed in breast cancers and renders the neoplastic disease resistant to established treatment, our findings are of clinical interest. (en)
- Zkoumali jsme, zda alfa-TOS a řada nových analogů vitamínu E zabíjí buňky nádoru prsu se zvýšenou expresí antiapoptotického receptorového proteinu HER2/erbB2. Zkoumané látky vyvolávaly apoptózu na srovnatelné úrovni u buněk s nízkou i vysokou hladinou erbB2. Před destabilizací mitochondrií a spuštěním apoptózy docházelo k tvorbě ROS. Ztrátu potenciálu delta-psí(m) následovala relokalizace cytochromu c a Smac/Diablo a také štěpení substrátu buněčné smrti závislé na kaspázách. Odolnost vůči apoptóze u odpovídajících protějšků rho(0) potvrdila kritickou závislost na mitochondriích během indukce apoptózy v buňkách nádoru prsu vyvolanou analogy VE a propojila apoptózu s tvorbou radikálů. Alfa-TOS tedy vyvolává účinnou apoptózu u buněk nádoru prsu nezávisle na jejich expresi erbB2. Jelikož exprese erbB2 je u nádoru prsu často zvýšena a vyvolává u neoplázií odolnost vůči zavedené léčbě, naše poznatky mají klinický význam. (cs)
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Title
| - Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway
- Analogy vitamínu E vyvolávají apoptózu v buňkách nádoru prsu se zvýšenou expresí HER2/erbB2 signalizací mitochondriální dráhou (cs)
- Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway (en)
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skos:prefLabel
| - Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway
- Analogy vitamínu E vyvolávají apoptózu v buňkách nádoru prsu se zvýšenou expresí HER2/erbB2 signalizací mitochondriální dráhou (cs)
- Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway (en)
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skos:notation
| - RIV/68378050:_____/05:00001362!RIV06-AV0-68378050
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http://linked.open.../vavai/riv/strany
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http://linked.open...avai/riv/aktivita
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http://linked.open...avai/riv/aktivity
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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/68378050:_____/05:00001362
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http://linked.open...riv/jazykVysledku
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http://linked.open.../riv/klicovaSlova
| - vitamin E analogs; apoptosis; ErbB2 (en)
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http://linked.open.../riv/klicoveSlovo
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http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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http://linked.open...ontrolniKodProRIV
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http://linked.open...i/riv/nazevZdroje
| - Biochemical and Biophysical Research Communications
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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...UplatneniVysledku
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http://linked.open...v/svazekPeriodika
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http://linked.open...iv/tvurceVysledku
| - Neužil, Jiří
- Salvatore, B. A.
- Witting, P. K.
- Wang, X.-F.
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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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