Anticancer activity of a Gold(I) phosphine thioredoxin reductase inhibitor in multiple myeloma

Thumbnail Image
File version

Version of Record (VoR)

Sze, Jun Hui
Raninga, Prahlad V
Nakamura, Kyohei
Casey, Mika
Khanna, Kum Kum
Berners-Price, Susan J
Di Trapani, Giovanna
Tonissen, Kathryn F
Primary Supervisor
Other Supervisors
File type(s)

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.

Journal Title

Redox Biology

Conference Title
Book Title


Thesis Type
Degree Program
Publisher link
Patent number
Grant identifier(s)
Rights Statement
Rights Statement

© 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 ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.

Item Access Status
Access the data
Related item(s)

Biochemistry and cell biology

Medical biochemistry and metabolomics

Pharmacology and pharmaceutical sciences

Medicinal and biomolecular chemistry

Persistent link to this record

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