Show simple item record

dc.contributor.authorM. Jellicoe, Matthewen_US
dc.contributor.authorJ. Nichols, Scotten_US
dc.contributor.authorA.Callus, Bernarden_US
dc.contributor.authorV.Baker, Murrayen_US
dc.contributor.authorJ.Barnard, Peteren_US
dc.contributor.authorJ. Berners-Price, Susanen_US
dc.contributor.authorWhelan, Jamesen_US
dc.contributor.authorC.Yeoh, Georgeen_US
dc.contributor.authorFilipovska, Aleksandraen_US
dc.date.accessioned2017-05-03T11:49:22Z
dc.date.available2017-05-03T11:49:22Z
dc.date.issued2008en_US
dc.date.modified2011-08-12T06:22:22Z
dc.identifier.issn01433334en_US
dc.identifier.doi10.1093/carcin/bgn093en_AU
dc.identifier.urihttp://hdl.handle.net/10072/39998
dc.description.abstractA hallmark of cancer cells is their ability to evade apoptosis and mitochondria play a critical role in this process. Delineating mitochondrial differences between normal and cancer cells has proven challenging due to the lack of matched cell lines. Here, we compare two matched liver progenitor cell (LPC) lines, one non-tumorigenic [p53-immortalized liver (PIL) 4] and the other tumorigenic (PIL2). Analysis of these cell lines and a p53 wild-type non-tumorigenic cell line [bipotential murine oval liver (BMOL)] revealed an increase in expression of genes encoding the antiapoptotic proteins cellular inhibitor of apoptosis protein (cIAP) 1 and yes associate protein in the PIL2 cells, which resulted in an increase in the protein encoded by these genes. PIL2 cells have higher mitochondrial membrane potential (??m) compared with PIL4 and BMOL and had greater levels of reactive oxygen species, despite the fact that the mitochondrial antioxidant enzyme, manganese superoxide disumutase, was elevated at transcript and protein levels. Taken together, these results may account for the observed resistance of PIL2 cells to apoptotic stimuli compared with PIL4. We tested a new gold compound to show that hyperpolarized ??m led to its increased accumulation in mitochondria of PIL2 cells. This compound selectively induces apoptosis in PIL2 cells but not in PIL4 or BMOL. The gold compound depolarized the ??m, depleted the adenosine triphosphate pool and activated caspase-3 and caspase-9, suggesting that apoptosis was mediated via mitochondria. This investigation shows that the non-tumorigenic and tumorigenic LPCs are useful models to delineate the role of mitochondrial dysfunction in tumorigenesis and for the future development of mitochondria-targeted chemotherapeutics that selectively target tumor cells.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherOxford University Pressen_US
dc.publisher.placeUnited Kingdomen_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom1124en_US
dc.relation.ispartofpageto1133en_US
dc.relation.ispartofissue6en_US
dc.relation.ispartofjournalCarcinogenesisen_US
dc.relation.ispartofvolume29en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchInorganic Chemistry not elsewhere classifieden_US
dc.subject.fieldofresearchcode030299en_US
dc.titleBioenergetic differences selectively sensitize tumorigenic liver progenitor cells to a new gold(I) compounden_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.date.issued2008
gro.hasfulltextNo Full Text


Files in this item

FilesSizeFormatView

There are no files associated with 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