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dc.contributor.authorO'Driscoll, Lorraineen
dc.contributor.authorPorter, Richarden
dc.date.accessioned2019-08-31T09:13:53Z
dc.date.available2019-08-31T09:13:53Z
dc.date.issued2019en
dc.date.submitted2019en
dc.identifier.citationO'Neill, S. and Porter, R.K., McNamee, N. and Martinez, V.G. and O'Driscoll, L., 2-Deoxy-D-Glucose inhibits aggressive triple-negative breast cancer cells by targeting glycolysis and the cancer stem cell phenotype, Scientific Reports, 9, 1, 2019, 3788 - 3798en
dc.identifier.otherYen
dc.identifier.urihttps://www.nature.com/articles/s41598-019-39789-9
dc.identifier.urihttp://hdl.handle.net/2262/89378
dc.descriptionPUBLISHEDen
dc.description10.1038/s41598-019-39789-9en
dc.description.abstractDue to limited availability of pharmacological therapies, triple-negative breast cancer (TNBC) is the subtype with worst outcome. We hypothesised that 2-Deoxy-D-Glucose (2-DG), a glucose analogue, may hold potential as a therapy for particularly aggressive TNBC. We investigated 2-DG’s effects on TNBC cell line variants, Hs578T parental cells and their isogenic more aggressive Hs578Ts(i)8 variant, using migration, invasion and anoikis assays. We assessed their bioenergetics by Seahorse. We evaluated metabolic alterations using a Seahorse XF Analyzer, citrate synthase assay, immunoblotting and flow cytometry. We assessed the cancer stem cell (CSC) phenotype of the variants and 2-DG’s effects on CSCs. 2-DG significantly inhibited migration and invasion of Hs578Ts(i)8 versus Hs578T and significantly decreased their ability to resist anoikis. Investigating 2-DG’s preferential inhibitory effect on the more aggressive cells, we found Hs578Ts(i)8 also had significantly decreased oxidative phosphorylation and increased glycolysis compared to Hs578T. This is likely due to mitochondrial dysfunction in Hs578Ts(i)8, shown by their significantly decreased mitochondrial membrane potential. Furthermore, Hs578Ts(i)8 had a significantly increased proportion of cells with CSC phenotype, which was significantly decreased by 2-DG. 2-DG may have benefit as a therapy for TNBC with a particularly aggressive phenotype, by targeting increased glycolysis. Studies of more cell lines and patients’ specimens are warranted.en
dc.format.extent3788en
dc.format.extent3798en
dc.language.isoenen
dc.relation.ispartofseriesScientific Reportsen
dc.relation.ispartofseries9en
dc.relation.ispartofseries1en
dc.rightsYen
dc.subjectTriple-negative breast cancer (TNBC)en
dc.subject2-Deoxy-D-Glucose (2-DG)en
dc.subjectCancer stem cell (CSC) phenotypeen
dc.subjectMetabolic alterationsen
dc.subjectSeahorse XF Analyzeren
dc.title2-Deoxy-D-Glucose inhibits aggressive triple-negative breast cancer cells by targeting glycolysis and the cancer stem cell phenotypeen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/rkporteren
dc.identifier.peoplefinderurlhttp://people.tcd.ie/lodriscen
dc.identifier.rssinternalid205984en
dc.identifier.doihttp://dx.doi.org/10.1038/s41598-019-39789-9en
dc.rights.ecaccessrightsopenAccess
dc.subject.TCDThemeCanceren
dc.subject.TCDTagExtracellular vesicles (EVs)en
dc.identifier.rssurihttps://www.ncbi.nlm.nih.gov/pubmed/30846710en
dc.identifier.orcid_id0000-0001-9854-5161en


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