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dc.contributor.authorSze, Jun Hui
dc.contributor.authorRaninga, Prahlad V
dc.contributor.authorNakamura, Kyohei
dc.contributor.authorCasey, Mika
dc.contributor.authorKhanna, Kum Kum
dc.contributor.authorBerners-Price, Susan J
dc.contributor.authorDi Trapani, Giovanna
dc.contributor.authorTonissen, Kathryn F
dc.date.accessioned2020-03-02T04:16:34Z
dc.date.available2020-03-02T04:16:34Z
dc.date.issued2020
dc.identifier.issn2213-2317
dc.identifier.doi10.1016/j.redox.2019.101310
dc.identifier.urihttp://hdl.handle.net/10072/387071
dc.description.abstractMultiple myeloma (MM), the second most common haematological malignancy, is a clonal plasma B-cell neoplasm that forms within the bone marrow. Despite recent advancements in treatment, MM remains an incurable disease. Auranofin, a linear gold(I) phosphine compound, has previously been shown to exert a significant anti-myeloma activity by inhibiting thioredoxin reductase (TrxR) activity. A bis-chelated tetrahedral gold(I) phosphine complex [Au(d2pype)2]Cl (where d2pype is 1,2-bis(di-2-pyridylphosphino)ethane) was previously designed to improve the gold(I) compound selectivity towards selenol- and thiol-containing proteins, such as TrxR. In this study, we show that [Au(d2pype)2]Cl significantly inhibited TrxR activity in both bortezomib-sensitive and resistant myeloma cells, which led to a significant reduction in cell proliferation and induction of apoptosis, both of which were dependent on ROS. In clonogenic assays, treatment with [Au(d2pype)2]Cl completely abrogated the tumourigenic capacity of MM cells, whereas auranofin was less effective. We also show that [Au(d2pype)2]Cl exerted a significant anti-myeloma activity in vivo in human RPMI8226 xenograft model in immunocompromised NOD/SCID mice. The MYC oncogene, known to drive myeloma progression, was downregulated in both in vitro and in vivo models when treated with [Au(d2pype)2]Cl. This study highlights the “proof of concept” that improved gold(I)-based compounds could potentially be used to not only treat MM but as an alternative tool to understand the role of the Trx system in the pathogenesis of this blood disease.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.publisher.placeNetherlands
dc.publisher.uriNetherlands
dc.relation.ispartofpagefrom101310:1
dc.relation.ispartofpageto101310:12
dc.relation.ispartofjournalRedox Biology
dc.relation.ispartofvolume28
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchMedical biochemistry and metabolomics
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3205
dc.subject.fieldofresearchcode3214
dc.subject.fieldofresearchcode3404
dc.titleAnticancer activity of a Gold(I) phosphine thioredoxin reductase inhibitor in multiple myeloma
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationSze, JH; Raninga, PV; Nakamura, K; Casey, M; Khanna, KK; Berners-Price, SJ; Di Trapani, G; Tonissen, KF, Anticancer activity of a Gold(I) phosphine thioredoxin reductase inhibitor in multiple myeloma, Redox Biology, 2019, pp. 101310:1-101310:12
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated2019-09-09T03:43:17Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2019 The Authors. Published by Elsevier B.V. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International (CC BY-NC-ND 4.0) License (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorBerners-Price, Sue J.
gro.griffith.authorDi Trapani, Jenny
gro.griffith.authorTonissen, Kathryn F.


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