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Statements

Subject Item
n2:RIV%2F68378050%3A_____%2F05%3A00001362%21RIV06-AV0-68378050
rdf:type
n12:Vysledek skos:Concept
dcterms: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. 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.
dcterms:title
Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway 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
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 Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway
skos:notation
RIV/68378050:_____/05:00001362!RIV06-AV0-68378050
n3:strany
282;289
n3:aktivita
n5:Z
n3:aktivity
Z(AV0Z5052915)
n3:cisloPeriodika
4
n3:dodaniDat
n4:2006
n3:domaciTvurceVysledku
n10:4589874
n3:druhVysledku
n7:J
n3:duvernostUdaju
n16:S
n3:entitaPredkladatele
n13:predkladatel
n3:idSjednocenehoVysledku
548951
n3:idVysledku
RIV/68378050:_____/05:00001362
n3:jazykVysledku
n11:eng
n3:klicovaSlova
vitamin E analogs; apoptosis; ErbB2
n3:klicoveSlovo
n9:vitamin%20E%20analogs n9:apoptosis n9:ErbB2
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[B5563FE9DE19]
n3:nazevZdroje
Biochemical and Biophysical Research Communications
n3:obor
n14:EB
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
4
n3:rokUplatneniVysledku
n4:2005
n3:svazekPeriodika
326
n3:tvurceVysledku
Salvatore, B. A. Wang, X.-F. Witting, P. K. Neužil, Jiří
n3:zamer
n15:AV0Z5052915
s:issn
0006-291X
s:numberOfPages
8