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dc.contributor.authorRaninga, Prahlad V
dc.contributor.authorDi Trapani, Giovanna
dc.contributor.authorVuckovic, Slavica
dc.contributor.authorBhatia, Maneet
dc.contributor.authorTonissen, Kathryn F
dc.date.accessioned2017-09-07T02:43:43Z
dc.date.available2017-09-07T02:43:43Z
dc.date.issued2015
dc.identifier.issn1949-2553
dc.identifier.doi10.18632/oncotarget.3795
dc.identifier.urihttp://hdl.handle.net/10072/116005
dc.description.abstractMultiple myeloma (MM) is a hematological malignancy characterized by the aberrant accumulation of clonal plasma cells in the bone marrow. Despite recent advancement in anti-myeloma treatment, MM remains an incurable disease. This study showed higher intrinsic oxidative stress and higher Trx1 and TrxR1 protein levels in MM cells compared to normal cells. Drug-induced Trx1 (PX-12) and TrxR1 (Auranofin) inhibition disrupted redox homeostasis resulting in ROS-induced apoptosis in MM cells and a reduction in clonogenic activity. Knockdown of either Trx1 or TrxR1 reduced MM cell viability. Trx1 inhibition by PX-12 sensitized MM cells to undergo apoptosis in response to the NF-?ߠinhibitors, BAY 11-7082 and curcumin. PX-12 treatment decreased the expression of the NF-?ߠsubunit p65 in MM cells. Bortezomib-resistant MM cells contained higher Trx1 protein levels compared to the parental cells and PX- 12 treatment resulted in apoptosis. Thus, increased Trx1 enhances MM cell growth and survival and exerts resistance to NF-?ߠinhibitors. Therefore inhibiting the thioredoxin system may be an effective therapeutic strategy to treat newly diagnosed as well as relapsed/refractory MM.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherImpact Journals LLC
dc.publisher.placeUnited States
dc.relation.ispartofpagefrom15410
dc.relation.ispartofpageto15424
dc.relation.ispartofissue17
dc.relation.ispartofjournalOncotarget
dc.relation.ispartofvolume6
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchCancer cell biology
dc.subject.fieldofresearchMolecular targets
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode321101
dc.subject.fieldofresearchcode321108
dc.titleInhibition of thioredoxin 1 leads to apoptosis in drug-resistant multiple myeloma
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/3.0/
dc.description.versionVersion of Record (VoR)
gro.facultyGriffith Sciences, Griffith Institute for Drug Discovery
gro.rights.copyright© The Author(s) 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorDi Trapani, Jenny
gro.griffith.authorTonissen, Kathryn F.


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