Show simple item record

dc.contributor.authorProchazka, Lubomiren_US
dc.contributor.authorDong, Lan-fengen_US
dc.contributor.authorValis, Karelen_US
dc.contributor.authorLambrechts, Ruthen_US
dc.contributor.authorRalph, Stephenen_US
dc.contributor.authorTuranek, Jaroslaven_US
dc.contributor.authorNeuzil, Jirien_US
dc.contributor.editorMels Sluyseren_US
dc.date.accessioned2017-05-03T14:15:02Z
dc.date.available2017-05-03T14:15:02Z
dc.date.issued2010en_US
dc.date.modified2011-03-08T06:49:11Z
dc.identifier.issn13608185en_US
dc.identifier.doi10.1007/s10495-010-0482-zen_AU
dc.identifier.urihttp://hdl.handle.net/10072/34071
dc.description.abstractMitocans are drugs selectively killing cancer cells by destabilizing mitochondria and many induce apoptosis via generation of reactive oxygen species (ROS). However, the molecular events by which ROS production leads to apoptosis has not been clearly defined. In this study with the mitocan a-tocopheryl succinate (a-TOS) the role of the Bcl-2 family proteins in the mechanism of malignant cell apoptosis has been determined. Exposure of several different cancer cell lines to a-TOS increased expression of the Noxa protein, but none of the other proteins of the Bcl-2 family, an event that was independent of the cellular p53 status. a-TOS caused a profound conformational change in the pro-apoptotic protein, Bak, involving oligomerization in all cell types, and this also applied to the Bax protein, but only in non-small cell lung cancer cells. Immunoprecipitation studies indicated that a-TOS activates the two BH1-3 proteins, Bak or Bax, to form high molecular weight complexes in the mitochondria. RNAi knockdown revealed that Noxa and Bak are required for a-TOS-induced apoptosis, and the role of Bak was confirmed using Bak- and/or Bax-deficient cells. We conclude that the major events induced by a-TOS in cancer cells downstream of ROS production leading to mitochondrial apoptosis involve the Noxa-Bak axis. It is proposed that this represents a common mechanism for mitochondrial destabilization activated by a variety of mitocans that induce accumulation of ROS in the early phases of apoptosis.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.format.extent162007 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherSpringeren_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom782en_US
dc.relation.ispartofpageto794en_US
dc.relation.ispartofissue7en_US
dc.relation.ispartofjournalApoptosisen_US
dc.relation.ispartofvolume15en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchCancer Cell Biologyen_US
dc.subject.fieldofresearchcode111201en_US
dc.titleα-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channelsen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightCopyright 2010 Springer Netherlands. This is an electronic version of an article published in Apoptosis Volume 15, Issue 7, 782-794, 2010 Apoptosis is available online at: http://www.informaworld.com/smpp/ with the open URL of your articleen_AU
gro.date.issued2010
gro.hasfulltextFull Text


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record