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dc.contributor.authorWang, XF
dc.contributor.authorWitting, PK
dc.contributor.authorSalvatore, BA
dc.contributor.authorNeuzil, J
dc.date.accessioned2017-05-03T12:22:08Z
dc.date.available2017-05-03T12:22:08Z
dc.date.issued2005
dc.date.modified2009-09-08T08:04:02Z
dc.identifier.issn0006-291X
dc.identifier.doi10.1016/j.bbrc.2004.11.028
dc.identifier.urihttp://hdl.handle.net/10072/4744
dc.description.abstracta-Tocopheryl succinate (a-TOS) is a redox-silent vitamin E (VE) analog with high pro-apoptotic and anti-neoplastic activity. Here we investigated whether a-TOS and several novel VE analogs kill breast cancer cells over-expressing the anti-apoptotic receptor protein HER2/erbB2. The agents induced apoptosis at comparable levels in both erbB2-low and -high cells. Generation of reactive oxygen species (ROS) preceded mitochondrial destabilization and execution of apoptosis, as evidenced by the anti-apoptotic effects of exogenous superoxide dismutase and mitochondrially targeted coenzyme Q. Dissipation of ??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 ?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 as judged by the delayed accumulation of ROS in the cybrid cell types. We conclude that a-TOS 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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAcademic Press
dc.publisher.placeUnited States
dc.publisher.urihttp://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description#description
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom282
dc.relation.ispartofpageto289
dc.relation.ispartofjournalBiochemical and biophysical research communications
dc.relation.ispartofvolume326
dc.rights.retentionY
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchMedical biochemistry and metabolomics
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3205
dc.titleVitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2005 Elsevier : Reproduced in accordance with the copyright policy of the publisher : This journal is available online - use hypertext links.
gro.date.issued2005
gro.hasfulltextNo Full Text
gro.griffith.authorNeuzil, Jiri


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