dc.contributor.author | Sze, Jun Hui | |
dc.contributor.author | Raninga, Prahlad V | |
dc.contributor.author | Nakamura, Kyohei | |
dc.contributor.author | Casey, Mika | |
dc.contributor.author | Khanna, Kum Kum | |
dc.contributor.author | Berners-Price, Susan J | |
dc.contributor.author | Di Trapani, Giovanna | |
dc.contributor.author | Tonissen, Kathryn F | |
dc.date.accessioned | 2020-03-02T04:16:34Z | |
dc.date.available | 2020-03-02T04:16:34Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 2213-2317 | |
dc.identifier.doi | 10.1016/j.redox.2019.101310 | |
dc.identifier.uri | http://hdl.handle.net/10072/387071 | |
dc.description.abstract | Multiple 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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.publisher.place | Netherlands | |
dc.publisher.uri | Netherlands | |
dc.relation.ispartofpagefrom | 101310:1 | |
dc.relation.ispartofpageto | 101310:12 | |
dc.relation.ispartofjournal | Redox Biology | |
dc.relation.ispartofvolume | 28 | |
dc.subject.fieldofresearch | Biochemistry and cell biology | |
dc.subject.fieldofresearch | Medical biochemistry and metabolomics | |
dc.subject.fieldofresearch | Pharmacology and pharmaceutical sciences | |
dc.subject.fieldofresearch | Medicinal and biomolecular chemistry | |
dc.subject.fieldofresearchcode | 3101 | |
dc.subject.fieldofresearchcode | 3205 | |
dc.subject.fieldofresearchcode | 3214 | |
dc.subject.fieldofresearchcode | 3404 | |
dc.title | Anticancer activity of a Gold(I) phosphine thioredoxin reductase inhibitor in multiple myeloma | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Sze, 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.license | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.date.updated | 2019-09-09T03:43:17Z | |
dc.description.version | Version 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.hasfulltext | Full Text | |
gro.griffith.author | Berners-Price, Sue J. | |
gro.griffith.author | Di Trapani, Jenny | |
gro.griffith.author | Tonissen, Kathryn F. | |