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dc.contributor.authorDong, Lan-Feng
dc.contributor.authorFreeman, Ruth
dc.contributor.authorLiu, Ji
dc.contributor.authorZobalova, Renata
dc.contributor.authorMarin-Hernandez, Alvaro
dc.contributor.authorStantic, Marina
dc.contributor.authorRohlena, Jakub
dc.contributor.authorValis, Karel
dc.contributor.authorRodriguez-Enriquez, Sara
dc.contributor.authorButcher, Bevan
dc.contributor.authorGoodwin, Jacob
dc.contributor.authorBrunk, Ulf T
dc.contributor.authorWitting, Paul K
dc.contributor.authorMoreno-Sanchez, Rafael
dc.contributor.authorScheffler, Immo E
dc.contributor.authorRalph, Stephen J
dc.contributor.authorNeuzil, Jiri
dc.date.accessioned2017-05-03T15:05:20Z
dc.date.available2017-05-03T15:05:20Z
dc.date.issued2009
dc.date.modified2010-06-07T08:05:53Z
dc.identifier.issn1078-0432
dc.identifier.doi10.1158/1078-0432.CCR-08-2439
dc.identifier.urihttp://hdl.handle.net/10072/30091
dc.description.abstractPurpose: Vitamin E analogues are potent novel anticancer drugs. The purpose of this study was to elucidate the cellular target by which these agents, represented by a-tocopoheryl succinate (a-TOS), suppress tumors in vivo, with the focus on the mitochondrial complex II (CII). Experimental Design: Chinese hamster lung fibroblasts with functional, dysfunctional, and reconstituted CII were transformed using H-Ras. The cells were then used to form xenografts in immunocompromized mice, and response of the cells and the tumors to a-TOS was studied. Results: The CII-functional and CII-reconstituted cells, unlike their CII-dysfunctional counterparts, responded to a-TOS by reactive oxygen species generation and apoptosis execution. Tumors derived from these cell lines reciprocated their responses to a-TOS. Thus, growth of CII-functional and CII-reconstituted tumors was strongly suppressed by the agent, and this was accompanied by high level of apoptosis induction in the tumor cells. On the other hand, a-TOS did not inhibit the CII-dysfuntional tumors. Conclusions: We document in this report a novel paradigm, according to which the mitochondrial CII, which rarely mutates in human neoplasias, is a plausible target for anticancer drugs from the group of vitamin E analogues, providing support for their testing in clinical trials.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent111326 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Association for Cancer Research
dc.publisher.placeUSA
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1593
dc.relation.ispartofpageto1600
dc.relation.ispartofissue5
dc.relation.ispartofjournalClinical Cancer Research
dc.relation.ispartofvolume15
dc.rights.retentionY
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchMolecular targets
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode321108
dc.subject.fieldofresearchcode3202
dc.titleSuppression of Tumor Growth In vivo by the Mitocan α-tocopheryl Succinate Requires Respiratory Complex II
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Medical Science
gro.rights.copyright© 2009 AACR. This is the author-manuscript version of the paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal link for access to the definitive, published version.
gro.date.issued2009
gro.hasfulltextFull Text
gro.griffith.authorNeuzil, Jiri
gro.griffith.authorRalph, Stephen J.


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