dc.contributor.author | Raninga, Prahlad V | |
dc.contributor.author | Di Trapani, Giovanna | |
dc.contributor.author | Vuckovic, Slavica | |
dc.contributor.author | Bhatia, Maneet | |
dc.contributor.author | Tonissen, Kathryn F | |
dc.date.accessioned | 2017-09-07T02:43:43Z | |
dc.date.available | 2017-09-07T02:43:43Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 1949-2553 | |
dc.identifier.doi | 10.18632/oncotarget.3795 | |
dc.identifier.uri | http://hdl.handle.net/10072/116005 | |
dc.description.abstract | Multiple 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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Impact Journals LLC | |
dc.publisher.place | United States | |
dc.relation.ispartofpagefrom | 15410 | |
dc.relation.ispartofpageto | 15424 | |
dc.relation.ispartofissue | 17 | |
dc.relation.ispartofjournal | Oncotarget | |
dc.relation.ispartofvolume | 6 | |
dc.subject.fieldofresearch | Oncology and carcinogenesis | |
dc.subject.fieldofresearch | Cancer cell biology | |
dc.subject.fieldofresearch | Molecular targets | |
dc.subject.fieldofresearchcode | 3211 | |
dc.subject.fieldofresearchcode | 321101 | |
dc.subject.fieldofresearchcode | 321108 | |
dc.title | Inhibition of thioredoxin 1 leads to apoptosis in drug-resistant multiple myeloma | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
dcterms.license | http://creativecommons.org/licenses/by/3.0/ | |
dc.description.version | Version of Record (VoR) | |
gro.faculty | Griffith 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.hasfulltext | Full Text | |
gro.griffith.author | Di Trapani, Jenny | |
gro.griffith.author | Tonissen, Kathryn F. | |