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dc.contributor.authorLiu, P
dc.contributor.authorWang, Z
dc.contributor.authorBrown, S
dc.contributor.authorKannappan, V
dc.contributor.authorTawari, PE
dc.contributor.authorJiang, W
dc.contributor.authorIrache, JM
dc.contributor.authorTang, JZ
dc.contributor.authorBritland, S
dc.contributor.authorArmesilla, AL
dc.contributor.authorDarling, JL
dc.contributor.authorTang, X
dc.contributor.authorWang, W
dc.date.accessioned2020-02-21T10:15:26Z
dc.date.available2020-02-21T10:15:26Z
dc.date.issued2014-07-04
dc.identifier.citationLiu, P., Wang, Z., Brown, S., Kannappan, V., Erebi Tawari, P., Jiang, W., Irache, J. M., Tang, J. Z., Britland, S., Armesilla, A. L, Darling, J. L., Tang, X.. and Wang, W. (2014) Liposome encapsulated Disulfiram inhibits NFκB pathway and targets breast cancer stem cells in vitro and in vivo, Oncotarget, 2014(5), pp. 7471-7485. https://doi.org/10.18632/oncotarget.2166en
dc.identifier.issn1949-2553en
dc.identifier.pmid25277186
dc.identifier.doi10.18632/oncotarget.2166en
dc.identifier.urihttp://hdl.handle.net/2436/623086
dc.description.abstractBreast cancer stem cells (BCSCs) are pan-resistant to different anticancer agents and responsible for cancer relapse. Disulfiram (DS), an antialcoholism drug, targets CSCs and reverses pan-chemoresistance. The anticancer application of DS is limited by its very short half-life in the bloodstream. This prompted us to develop a liposome-encapsulated DS (Lipo-DS) and examine its anticancer effect and mechanisms in vitro and in vivo. The relationship between hypoxia and CSCs was examined by in vitro comparison of BC cells cultured in spheroid and hypoxic conditions. To determine the importance of NFκB activation in bridging hypoxia and CSC-related pan-resistance, the CSC characters and drug sensitivity in BC cell lines were observed in NFκB p65 transfected cell lines. The effect of Lipo-DS on the NFκB pathway, CSCs and chemosensitivity was investigated in vitro and in vivo. The spheroid cultured BC cells manifested CSC characteristics and pan-resistance to anticancer drugs. This was related to the hypoxic condition in the spheres. Hypoxia induced activation of NFκB and chemoresistance. Transfection of BC cells with NFκB p65 also induced CSC characters and pan-resistance. Lipo-DS blocked NFκB activation and specifically targeted CSCs in vitro. Lipo-DS also targeted the CSC population in vivo and showed very strong anticancer efficacy. Mice tolerated the treatment very well and no significant in vivo nonspecific toxicity was observed. Hypoxia induced NFκB activation is responsible for stemness and chemoresistance in BCSCs. Lipo-DS targets NFκB pathway and CSCs. Further study may translate DS into cancer therapeutics.en
dc.description.sponsorshipThis project was supported by Breast Cancer Campaign (UK) and Marie-Curie IIF Program (PIIF-GA-2013-629478).en
dc.formatapplication/pdfen
dc.languageeng
dc.language.isoenen
dc.publisherImpact Journalsen
dc.relation.urlhttp://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=2166&path[]=3427en
dc.rightsLicence for published version: Creative Commons Attribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBreast canceren
dc.subjectCancer stem cellsen
dc.subjectDisulfiramen
dc.subjectNFkappaBen
dc.subjectChemoresistanceen
dc.titleLiposome encapsulated Disulfiram inhibits NFκB pathway and targets breast cancer stem cells in vitro and in vivoen
dc.typeJournal articleen
dc.identifier.journalOncotargeten
dc.date.updated2020-02-20T17:16:03Z
dc.contributor.institutionResearch Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK.
pubs.place-of-publicationUnited States
dc.date.accepted2014-07-03
rioxxterms.funderBreast Cancer Campaign (UK) and Marie-Curie IIF Program
rioxxterms.identifier.project2010NOVSP13en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2020-02-21en
dc.source.volume5
dc.source.issue17
dc.source.beginpage7471
dc.source.endpage7485
dc.description.versionPublished version
refterms.dateFCD2020-02-21T10:14:38Z
refterms.versionFCDVoR
refterms.dateFOA2020-02-21T10:15:27Z


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Licence for published version: Creative Commons Attribution 4.0 International
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