Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Discover Oncology
Published in: Discover Oncology 1/2021

Open Access 01-12-2021 | Auranofin | Perspective

The gold complex auranofin: new perspectives for cancer therapy

Authors: Farah H. Abdalbari, Carlos M. Telleria

Published in: Discover Oncology | Issue 1/2021

Login to get access

Abstract

Advanced stages of cancer are highly associated with short overall survival in patients due to the lack of long-term treatment options following the standard form of care. New options for cancer therapy are needed to improve the survival of cancer patients without disease recurrence. Auranofin is a clinically approved agent against rheumatoid arthritis that is currently enrolled in clinical trials for potential repurposing against cancer. Auranofin mainly targets the anti-oxidative system catalyzed by thioredoxin reductase (TrxR), which protects the cell from oxidative stress and death in the cytoplasm and the mitochondria. TrxR is over-expressed in many cancers as an adaptive mechanism for cancer cell proliferation, rendering it an attractive target for cancer therapy, and auranofin as a potential therapeutic agent for cancer. Inhibiting TrxR dysregulates the intracellular redox state causing increased intracellular reactive oxygen species levels, and stimulates cellular demise. An alternate mechanism of action of auranofin is to mimic proteasomal inhibition by blocking the ubiquitin–proteasome system (UPS), which is critically important in cancer cells to prevent cell death when compared to non-cancer cells, because of its role on cell cycle regulation, protein degradation, gene expression, and DNA repair. This article provides new perspectives on the potential mechanisms used by auranofin alone, in combination with diverse other compounds, or in combination with platinating agents and/or immune checkpoint inhibitors to combat cancer cells, while assessing the feasibility for its repurposing in the clinical setting.
Literature
1.
Sutton BM, McGusty E, Walz DT, DiMartino MJ. Oral gold. Antiarthritic properties of alkylphosphinegold coordination complexes. J Med Chem. 1972;15(11):1095–8.PubMedCrossRef
2.
Berners-Price SJ, Filipovska A. Gold compounds as therapeutic agents for human diseases. Metallomics. 2011;3(9):863–73.PubMedCrossRef
3.
Crooke ST, Snyder RM, Butt TR, Ecker DJ, Allaudeen HS, Monia B, Mirabelli CK. Cellular and molecular pharmacology of auranofin and related gold complexes. Biochem Pharmacol. 1986;35(20):3423–31.PubMedCrossRef
4.
Kupiec M, Ziolkowski R, Massai L, Messori L, Pawlak K. The electrochemical profiles of Auranofin and Aubipy(c), two representative medicinal gold compounds: a comparative study. J Inorg Biochem. 2019;198:110714.PubMedCrossRef
5.
Zoppi C, Messori L, Pratesi A. ESI MS studies highlight the selective interaction of Auranofin with protein free thiols. Dalton Trans. 2020;49(18):5906–13.PubMedCrossRef
6.
Nobili S, Mini E, Landini I, Gabbiani C, Casini A, Messori L. Gold compounds as anticancer agents: chemistry, cellular pharmacology, and preclinical studies. Med Res Rev. 2010;30(3):550–80.PubMedCrossRef
7.
Go YM, Roede JR, Walker DI, Duong DM, Seyfried NT, Orr M, Liang Y, Pennell KD, Jones DP. Selective targeting of the cysteine proteome by thioredoxin and glutathione redox systems. Mol Cell Proteomics. 2013;12(11):3285–96.PubMedPubMedCentralCrossRef
8.
Magherini F, Modesti A, Bini L, Puglia M, Landini I, Nobili S, Mini E, Cinellu MA, Gabbiani C, Messori L. Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study. J Biol Inorg Chem. 2010;15(4):573–82.PubMedCrossRef
9.
Englinger B, Pirker C, Heffeter P, Terenzi A, Kowol CR, Keppler BK, Berger W. Metal drugs and the anticancer immune response. Chem Rev. 2019;119(2):1519–624.PubMedCrossRef
10.
Wu B, Yang X, Yan M. Synthesis and structure–activity relationship study of antimicrobial auranofin against ESKAPE pathogens. J Med Chem. 2019;62(17):7751–68.PubMedPubMedCentralCrossRef
11.
Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. ChEBI in 2016: improved services and an expanding collection of metabolites. Nucleic Acids Res. 2016;44(D1):D1214-1219.PubMedCrossRef
12.
Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4:18001.PubMedCrossRef
13.
Bullock J, Rizvi SAA, Saleh AM, Ahmed SS, Do DP, Ansari RA, Ahmed J. Rheumatoid arthritis: a brief overview of the treatment. Med Princ Pract. 2018;27(6):501–7.PubMedPubMedCentralCrossRef
14.
15.
Ramiro S, Gaujoux-Viala C, Nam JL, Smolen JS, Buch M, Gossec L, van der Heijde D, Winthrop K, Landewe R. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2014;73(3):529–35.PubMedCrossRef
16.
17.
Davis P, Johnston C. Effects of gold compounds on function of phagocytic cells. Comparative inhibition of activated polymorphonuclear leukocytes and monocytes from rheumatoid arthritis and control subjects. Inflammation. 1986;10(3):311–20.PubMedCrossRef
18.
Furst DE. Mechanism of action, pharmacology, clinical efficacy and side effects of auranofin. An orally administered organic gold compound for the treatment of rheumatoid arthritis. Pharmacotherapy. 1983;3(5):284–98.PubMedCrossRef
19.
20.
Chaffman M, Brogden RN, Heel RC, Speight TM, Avery GS. Auranofin. A preliminary review of its pharmacological properties and therapeutic use in rheumatoid arthritis. Drugs. 1984;27(5):378–424.PubMedCrossRef
21.
Han S, Kim K, Kim H, Kwon J, Lee YH, Lee CK, Song Y, Lee SJ, Ha N, Kim K. Auranofin inhibits overproduction of pro-inflammatory cytokines, cyclooxygenase expression and PGE2 production in macrophages. Arch Pharm Res. 2008;31(1):67–74.PubMedCrossRef
22.
Kim NH, Lee MY, Park SJ, Choi JS, Oh MK, Kim IS. Auranofin blocks interleukin-6 signalling by inhibiting phosphorylation of JAK1 and STAT3. Immunology. 2007;122(4):607–14.PubMedPubMedCentralCrossRef
23.
Yamada R, Sano H, Hla T, Hashiramoto A, Fukui W, Miyazaki S, Kohno M, Tsubouchi Y, Kusaka Y, Kondo M. Auranofin inhibits interleukin-1beta-induced transcript of cyclooxygenase-2 on cultured human synoviocytes. Eur J Pharmacol. 1999;385(1):71–9.PubMedCrossRef
24.
Jeon KI, Jeong JY, Jue DM. Thiol-reactive metal compounds inhibit NF-kappa B activation by blocking I kappa B kinase. J Immunol. 2000;164(11):5981–9.PubMedCrossRef
25.
Nathan I, Finkelstein AE, Walz DT, Dvilansky A. Studies of the effect of auranofin, a new antiarthritic agent, on platelet aggregation. Inflammation. 1982;6(1):79–85.PubMedCrossRef
26.
Fantini F, Cottafava F, Martini A, Murelli M, Franchini E, D’Errico R, Panzarasa R. Changes of immunological parameters during auranofin treatment in children affected with juvenile chronic arthritis. Int J Clin Pharmacol Res. 1986;6(1):61–7.PubMed
27.
Hwangbo H, Ji SY, Kim MY, Kim SY, Lee H, Kim GY, Kim S, Cheong J, Choi YH. Anti-inflammatory effect of auranofin on palmitic acid and LPS-induced inflammatory response by modulating TLR4 and NOX4-mediated NF-kappaB signaling pathway in RAW264.7 macrophages. Int J Mol Sci. 2021;22(11):5920.PubMedPubMedCentralCrossRef
28.
29.
Saikolappan S, Kumar B, Shishodia G, Koul S, Koul HK. Reactive oxygen species and cancer: a complex interaction. Cancer Lett. 2019;452:132–43.PubMedCrossRef
30.
Arner ES, Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem. 2000;267(20):6102–9.PubMedCrossRef
31.
Bindoli A, Rigobello MP, Scutari G, Gabbiani C, Casini A, Messori L. Thioredoxin reductase: a target for gold compounds acting as potential anticancer drugs. Coord Chem Rev. 2009;253:1692–707.CrossRef
32.
Marzano C, Gandin V, Folda A, Scutari G, Bindoli A, Rigobello MP. Inhibition of thioredoxin reductase by auranofin induces apoptosis in cisplatin-resistant human ovarian cancer cells. Free Radic Biol Med. 2007;42(6):872–81.PubMedCrossRef
33.
Casini A, Hartinger C, Gabbiani C, Mini E, Dyson PJ, Keppler BK, Messori L. Gold(III) compounds as anticancer agents: relevance of gold-protein interactions for their mechanism of action. J Inorg Biochem. 2008;102(3):564–75.PubMedCrossRef
34.
Barnard PJ, Berners-Price SJ. Targeting the mitochondrial cell death pathway with gold compounds. Coord Chem Rev. 2007;251:1889–902.CrossRef
35.
Rackham O, Shearwood AM, Thyer R, McNamara E, Davies SM, Callus BA, Miranda-Vizuete A, Berners-Price SJ, Cheng Q, Arner ES, et al. Substrate and inhibitor specificities differ between human cytosolic and mitochondrial thioredoxin reductases: implications for development of specific inhibitors. Free Radic Biol Med. 2011;50(6):689–99.PubMedCrossRef
36.
37.
Arner ESJ. Targeting the selenoprotein thioredoxin reductase 1 for anticancer therapy. Adv Cancer Res. 2017;136:139–51.PubMedCrossRef
38.
Karlenius TC, Tonissen KF. Thioredoxin and cancer: a role for thioredoxin in all states of tumor oxygenation. Cancers (Basel). 2010;2(2):209–32.CrossRef
39.
Mohammadi F, Soltani A, Ghahremanloo A, Javid H, Hashemy SI. The thioredoxin system and cancer therapy: a review. Cancer Chemother Pharmacol. 2019;84(5):925–35.PubMedCrossRef
40.
Onodera T, Momose I, Kawada M. Potential anticancer activity of auranofin. Chem Pharm Bull (Tokyo). 2019;67(3):186–91.CrossRef
41.
Meuillet EJ, Mahadevan D, Berggren M, Coon A, Powis G. Thioredoxin-1 binds to the C2 domain of PTEN inhibiting PTEN’s lipid phosphatase activity and membrane binding: a mechanism for the functional loss of PTEN’s tumor suppressor activity. Arch Biochem Biophys. 2004;429(2):123–33.PubMedCrossRef
42.
Gasdaska PY, Oblong JE, Cotgreave IA, Powis G. The predicted amino acid sequence of human thioredoxin is identical to that of the autocrine growth factor human adult T-cell derived factor (ADF): thioredoxin mRNA is elevated in some human tumors. Biochim Biophys Acta. 1994;1218(3):292–6.PubMedCrossRef
43.
Lim JY, Yoon SO, Hong SW, Kim JW, Choi SH, Cho JY. Thioredoxin and thioredoxin-interacting protein as prognostic markers for gastric cancer recurrence. World J Gastroenterol. 2012;18(39):5581–8.PubMedPubMedCentralCrossRef
44.
Nakamura H, Bai J, Nishinaka Y, Ueda S, Sasada T, Ohshio G, Imamura M, Takabayashi A, Yamaoka Y, Yodoi J. Expression of thioredoxin and glutaredoxin, redox-regulating proteins, in pancreatic cancer. Cancer Detect Prev. 2000;24(1):53–60.PubMed
45.
Raffel J, Bhattacharyya AK, Gallegos A, Cui H, Einspahr JG, Alberts DS, Powis G. Increased expression of thioredoxin-1 in human colorectal cancer is associated with decreased patient survival. J Lab Clin Med. 2003;142(1):46–51.PubMedCrossRef
46.
Lincoln DT, Ali Emadi EM, Tonissen KF, Clarke FM. The thioredoxin–thioredoxin reductase system: over-expression in human cancer. Anticancer Res. 2003;23(3B):2425–33.PubMed
47.
Narayanan D, Ma S, Ozcelik D. Targeting the redox landscape in cancer therapy. Cancers (Basel). 2020;12(7):1706.CrossRef
48.
Purohit V, Simeone DM, Lyssiotis CA. Metabolic regulation of redox balance in cancer. Cancers (Basel). 2019;11(7):955.CrossRef
49.
Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009;8(7):579–91.PubMedCrossRef
50.
Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, Castoria G, Migliaccio A. ROS in cancer therapy: the bright side of the moon. Exp Mol Med. 2020;52(2):192–203.PubMedPubMedCentralCrossRef
51.
Srinivas US, Tan BWQ, Vellayappan BA, Jeyasekharan AD. ROS and the DNA damage response in cancer. Redox Biol. 2019;25:101084.PubMedCrossRef
52.
Hedstrom E, Eriksson S, Zawacka-Pankau J, Arner ES, Selivanova G. p53-dependent inhibition of TrxR1 contributes to the tumor-specific induction of apoptosis by RITA. Cell Cycle (Georgetown, Tex). 2009;8(21):3584–91.CrossRef
53.
54.
Arner ES, Nakamura H, Sasada T, Yodoi J, Holmgren A, Spyrou G. Analysis of the inhibition of mammalian thioredoxin, thioredoxin reductase, and glutaredoxin by cis-diamminedichloroplatinum (II) and its major metabolite, the glutathione-platinum complex. Free Radic Biol Med. 2001;31(10):1170–8.PubMedCrossRef
55.
Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer. 2007;7(8):573–84.PubMedCrossRef
56.
Rottenberg S, Disler C, Perego P. The rediscovery of platinum-based cancer therapy. Nat Rev Cancer. 2021;21(1):37–50.PubMedCrossRef
57.
Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 2006;6(1):38–51.PubMedCrossRef
58.
You BR, Park WH. Suberoylanilide hydroxamic acid induces thioredoxin1-mediated apoptosis in lung cancer cells via up-regulation of miR-129-5p. Mol Carcinog. 2017;56(12):2566–77.PubMedCrossRef
59.
Morley N, Curnow A, Salter L, Campbell S, Gould D. N-acetyl-l-cysteine prevents DNA damage induced by UVA, UVB and visible radiation in human fibroblasts. J Photochem Photobiol B. 2003;72(1–3):55–60.PubMedCrossRef
60.
Kurashige T, Shimamura M, Nagayama Y. N-Acetyl-l-cysteine protects thyroid cells against DNA damage induced by external and internal irradiation. Radiat Environ Biophys. 2017;56(4):405–12.PubMedCrossRef
61.
Sobhakumari A, Love-Homan L, Fletcher EV, Martin SM, Parsons AD, Spitz DR, Knudson CM, Simons AL. Susceptibility of human head and neck cancer cells to combined inhibition of glutathione and thioredoxin metabolism. PLoS ONE. 2012;7(10):e48175.PubMedPubMedCentralCrossRef
62.
You BR, Park WH. Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion. Oncol Rep. 2016;35(1):546–51.PubMedCrossRef
63.
Oommen D, Dodd NJ, Yiannakis D, Moyeed R, Jha AN. Linking genotoxicity and cytotoxicity with membrane fluidity: a comparative study in ovarian cancer cell lines following exposure to auranofin. Mutat Res. 2016;809:43–9.CrossRef
64.
Li H, Hu J, Wu S, Wang L, Cao X, Zhang X, Dai B, Cao M, Shao R, Zhang R, et al. Auranofin-mediated inhibition of PI3K/AKT/mTOR axis and anticancer activity in non-small cell lung cancer cells. Oncotarget. 2016;7(3):3548–58.PubMedCrossRef
65.
Rios Perez MV, Roife D, Dai B, Pratt M, Dobrowolski R, Kang Y, Li X, Augustine JJ, Zielinski R, Priebe W, et al. Antineoplastic effects of auranofin in human pancreatic adenocarcinoma preclinical models. Surg Open Sci. 2019;1(2):56–63.PubMedPubMedCentralCrossRef
66.
Liu N, Li X, Huang H, Zhao C, Liao S, Yang C, Liu S, Song W, Lu X, Lan X, et al. Clinically used antirheumatic agent auranofin is a proteasomal deubiquitinase inhibitor and inhibits tumor growth. Oncotarget. 2014;5(14):5453–71.PubMedPubMedCentralCrossRef
67.
Fhu CW, Ali A. Dysregulation of the ubiquitin proteasome system in human malignancies: a window for therapeutic intervention. Cancers (Basel). 2021;13(7):1513.CrossRef
68.
Guidi F, Landini I, Puglia M, Magherini F, Gabbiani C, Cinellu MA, Nobili S, Fiaschi T, Bini L, Mini E, et al. Proteomic analysis of ovarian cancer cell responses to cytotoxic gold compounds. Metallomics. 2012;4(3):307–14.PubMedCrossRef
69.
70.
Chen X, Shi X, Wang X, Liu J. Novel use of old drug: anti-rheumatic agent auranofin overcomes imatinib-resistance of chronic myeloid leukemia cells. Cancer Cell Microenviron. 2014;1(6).
71.
Park SH, Lee JH, Berek JS, Hu MC. Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53. Int J Oncol. 2014;45(4):1691–8.PubMedPubMedCentralCrossRef
72.
Wang J, Wang J, Lopez E, Guo H, Zhang H, Liu Y, Chen Z, Huang S, Zhou S, Leeming A, et al. Repurposing auranofin to treat TP53-mutated or PTEN-deleted refractory B-cell lymphoma. Blood Cancer J. 2019;9(12):95.PubMedPubMedCentralCrossRef
73.
Oommen D, Yiannakis D, Jha AN. BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin. Mutat Res. 2016;784–785:8–15.PubMedCrossRef
74.
Langdon SP, Lawrie SS, Hay FG, Hawkes MM, McDonald A, Hayward IP, Schol DJ, Hilgers J, Leonard RC, Smyth JF. Characterization and properties of nine human ovarian adenocarcinoma cell lines. Cancer Res. 1988;48(21):6166–72.PubMed
75.
Cooke SL, Ng CK, Melnyk N, Garcia MJ, Hardcastle T, Temple J, Langdon S, Huntsman D, Brenton JD. Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma. Oncogene. 2010;29(35):4905–13.PubMedPubMedCentralCrossRef
76.
Abdalbari FH, Goyeneche AA, Martinez-Jaramillo E, Sabri S, Telleria CM. Repurposing the anti-rheumatic gold compound auranofin for high-grade serous ovarian cancer. Cancer Res (Virtual: AACR). 2021;81(13):1014–1014.
77.
Sachweh MC, Stafford WC, Drummond CJ, McCarthy AR, Higgins M, Campbell J, Brodin B, Arner ES, Lain S. Redox effects and cytotoxic profiles of MJ25 and auranofin towards malignant melanoma cells. Oncotarget. 2015;6(18):16488–506.PubMedPubMedCentralCrossRef
78.
Harris IS, Treloar AE, Inoue S, Sasaki M, Gorrini C, Lee KC, Yung KY, Brenner D, Knobbe-Thomsen CB, Cox MA, et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell. 2015;27(2):211–22.PubMedCrossRef
79.
Karsa M, Kosciolek A, Bongers A, Mariana A, Failes T, Gifford AJ, Kees UR, Cheung LC, Kotecha RS, Arndt GM, et al. Exploiting the reactive oxygen species imbalance in high-risk paediatric acute lymphoblastic leukaemia through auranofin. Br J Cancer. 2021;125(1):55–64.PubMedCrossRefPubMedCentral
80.
Zhang Q, Chen W, Lv X, Weng Q, Chen M, Cui R, Liang G, Ji J. Piperlongumine, a novel TrxR1 inhibitor, induces apoptosis in hepatocellular carcinoma cells by ROS-mediated ER stress. Front Pharmacol. 2019;10:1180.PubMedPubMedCentralCrossRef
81.
Zhang D, Liu Y, Luo Z, Chen Y, Xu A, Liang Y, Wu B, Tong X, Liu X, Shen H, et al. The novel thioredoxin reductase inhibitor A-Z2 triggers intrinsic apoptosis and shows efficacy in the treatment of acute myeloid leukemia. Free Radic Biol Med. 2020;146:275–86.PubMedCrossRef
82.
Casini A, Messori L. Molecular mechanisms and proposed targets for selected anticancer gold compounds. Curr Top Med Chem. 2011;11(21):2647–60.PubMedCrossRef
83.
Berners-Price SJ, Mirabelli CK, Johnson RK, Mattern MR, McCabe FL, Faucette LF, Sung CM, Mong SM, Sadler PJ, Crooke ST. In vivo antitumor activity and in vitro cytotoxic properties of bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride. Cancer Res. 1986;46(11):5486–93.PubMed
84.
Humphreys AS, Filipovska A, Berners-Price SJ, Koutsantonis GA, Skelton BW, White AH. Gold(I) chloride adducts of 1,3-bis(di-2-pyridylphosphino)propane: synthesis, structural studies and antitumour activity. Dalton Trans. 2007;43:4943–50.CrossRef
85.
Rackham O, Nichols SJ, Leedman PJ, Berners-Price SJ, Filipovska A. A gold(I) phosphine complex selectively induces apoptosis in breast cancer cells: implications for anticancer therapeutics targeted to mitochondria. Biochem Pharmacol. 2007;74(7):992–1002.PubMedCrossRef
86.
Caruso F, Villa R, Rossi M, Pettinari C, Paduano F, Pennati M, Daidone MG, Zaffaroni N. Mitochondria are primary targets in apoptosis induced by the mixed phosphine gold species chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I) in melanoma cell lines. Biochem Pharmacol. 2007;73(6):773–81.PubMedCrossRef
87.
Pillarsetty N, Katti KK, Hoffman TJ, Volkert WA, Katti KV, Kamei H, Koide T. In vitro and in vivo antitumor properties of tetrakis((trishydroxy-methyl)phosphine)gold(I) chloride. J Med Chem. 2003;46(7):1130–2.PubMedCrossRef
88.
Baker MV, Barnard PJ, Berners-Price SJ, Brayshaw SK, Hickey JL, Skelton BW, White AH. Cationic, linear Au(I) N-heterocyclic carbene complexes: synthesis, structure and anti-mitochondrial activity. Dalton Trans. 2006;30:3708–15.CrossRef
89.
Magherini F, Fiaschi T, Valocchia E, Becatti M, Pratesi A, Marzo T, Massai L, Gabbiani C, Landini I, Nobili S, et al. Antiproliferative effects of two gold(I)-N-heterocyclic carbene complexes in A2780 human ovarian cancer cells: a comparative proteomic study. Oncotarget. 2018;9(46):28042–68.PubMedPubMedCentralCrossRef
90.
Gandin V, Fernandes AP, Rigobello MP, Dani B, Sorrentino F, Tisato F, Bjornstedt M, Bindoli A, Sturaro A, Rella R, et al. Cancer cell death induced by phosphine gold(I) compounds targeting thioredoxin reductase. Biochem Pharmacol. 2010;79(2):90–101.PubMedCrossRef
91.
Marzo T, Cirri D, Gabbiani C, Gamberi T, Magherini F, Pratesi A, Guerri A, Biver T, Binacchi F, Stefanini M, et al. Auranofin, Et3PAuCl, and Et3PAuI are highly cytotoxic on colorectal cancer cells: a chemical and biological study. ACS Med Chem Lett. 2017;8(10):997–1001.PubMedPubMedCentralCrossRef
92.
Marzo T, Massai L, Pratesi A, Stefanini M, Cirri D, Magherini F, Becatti M, Landini I, Nobili S, Mini E, et al. Replacement of the thiosugar of auranofin with iodide enhances the anticancer potency in a mouse model of ovarian cancer. ACS Med Chem Lett. 2019;10(4):656–60.PubMedPubMedCentralCrossRef
93.
Tolbatov I, Cirri D, Marchetti L, Marrone A, Coletti C, Re N, La Mendola D, Messori L, Marzo T, Gabbiani C, et al. Mechanistic insights into the anticancer properties of the auranofin analog Au(PEt3)I: a theoretical and experimental study. Front Chem. 2020;8:812.PubMedPubMedCentralCrossRef
94.
Landini I, Massai L, Cirri D, Gamberi T, Paoli P, Messori L, Mini E, Nobili S. Structure–activity relationships in a series of auranofin analogues showing remarkable antiproliferative properties. J Inorg Biochem. 2020;208:111079.PubMedCrossRef
95.
Cirri D, Fabbrini MG, Massai L, Pillozzi S, Guerri A, Menconi A, Messori L, Marzo T, Pratesi A. Structural and solution chemistry, antiproliferative effects, and serum albumin binding of three pseudohalide derivatives of auranofin. Biometals. 2019;32(6):939–48.PubMedCrossRef
96.
Hou GX, Liu PP, Zhang S, Yang M, Liao J, Yang J, Hu Y, Jiang WQ, Wen S, Huang P. Elimination of stem-like cancer cell side-population by auranofin through modulation of ROS and glycolysis. Cell Death Dis. 2018;9(2):89.PubMedPubMedCentralCrossRef
97.
Yan X, Zhang X, Wang L, Zhang R, Pu X, Wu S, Li L, Tong P, Wang J, Meng QH, et al. Inhibition of thioredoxin/thioredoxin reductase induces synthetic lethality in lung cancers with compromised glutathione homeostasis. Cancer Res. 2019;79(1):125–32.PubMedCrossRef
98.
Landini I, Lapucci A, Pratesi A, Massai L, Napoli C, Perrone G, Pinzani P, Messori L, Mini E, Nobili S. Selection and characterization of a human ovarian cancer cell line resistant to auranofin. Oncotarget. 2017;8(56):96062–78.PubMedPubMedCentralCrossRef
99.
Graczyk-Jarzynka A, Goral A, Muchowicz A, Zagozdzon R, Winiarska M, Bajor M, Trzeciecka A, Fidyt K, Krupka JA, Cyran J, et al. Inhibition of thioredoxin-dependent H2O2 removal sensitizes malignant B-cells to pharmacological ascorbate. Redox Biol. 2019;21:101062.PubMedCrossRef
100.
Yang L, Wang H, Yang X, Wu Q, An P, Jin X, Liu W, Huang X, Li Y, Yan S, et al. Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms. Signal Transduct Target Ther. 2020;5(1):138.PubMedPubMedCentralCrossRef
101.
Yumnamcha T, Devi TS, Singh LP. Auranofin mediates mitochondrial dysregulation and inflammatory cell death in human retinal pigment epithelial cells: implications of retinal neurodegenerative diseases. Front Neurosci. 2019;13:1065.PubMedPubMedCentralCrossRef
102.
Fan C, Zheng W, Fu X, Li X, Wong YS, Chen T. Enhancement of auranofin-induced lung cancer cell apoptosis by selenocystine, a natural inhibitor of TrxR1 in vitro and in vivo. Cell Death Dis. 2014;5:e1191.PubMedPubMedCentralCrossRef
103.
Zou P, Chen M, Ji J, Chen W, Chen X, Ying S, Zhang J, Zhang Z, Liu Z, Yang S, et al. Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer. Oncotarget. 2015;6(34):36505–21.PubMedPubMedCentralCrossRef
104.
Rigobello MP, Gandin V, Folda A, Rundlof AK, Fernandes AP, Bindoli A, Marzano C, Bjornstedt M. Treatment of human cancer cells with selenite or tellurite in combination with auranofin enhances cell death due to redox shift. Free Radic Biol Med. 2009;47(6):710–21.PubMedCrossRef
105.
Rigobello MP, Scutari G, Boscolo R, Bindoli A. Induction of mitochondrial permeability transition by auranofin, a gold(I)-phosphine derivative. Br J Pharmacol. 2002;136(8):1162–8.PubMedPubMedCentralCrossRef
106.
Lee JE, Kwon YJ, Baek HS, Ye DJ, Cho E, Choi HK, Oh KS, Chun YJ. Synergistic induction of apoptosis by combination treatment with mesupron and auranofin in human breast cancer cells. Arch Pharm Res. 2017;40(6):746–59.PubMedCrossRef
107.
Han Y, Chen P, Zhang Y, Lu W, Ding W, Luo Y, Wen S, Xu R, Liu P, Huang P. Synergy between auranofin and celecoxib against colon cancer in vitro and in vivo through a novel redox-mediated mechanism. Cancers (Basel). 2019:11(7).
108.
Ehrenfeld V, Heusel JR, Fulda S, van Wijk SJL. ATM inhibition enhances Auranofin-induced oxidative stress and cell death in lung cell lines. PLoS ONE. 2020;15(12):e0244060.PubMedPubMedCentralCrossRef
109.
Krabbendam IE, Honrath B, Bothof L, Silva-Pavez E, Huerta H, Penaranda Fajardo NM, Dekker F, Schmidt M, Culmsee C, Cesar Cardenas J, et al. SK channel activation potentiates auranofin-induced cell death in glio- and neuroblastoma cells. Biochem Pharmacol. 2020;171:113714.PubMedCrossRef
110.
Weatherall KL, Goodchild SJ, Jane DE, Marrion NV. Small conductance calcium-activated potassium channels: from structure to function. Prog Neurobiol. 2010;91(3):242–55.PubMedCrossRef
111.
Joo MK, Shin S, Ye DJ, An HG, Kwon TU, Baek HS, Kwon YJ, Chun YJ. Combined treatment with auranofin and trametinib induces synergistic apoptosis in breast cancer cells. J Toxicol Environ Health A. 2021;84(2):84–94.PubMedCrossRef
112.
Hyter S, Hirst J, Pathak H, Pessetto ZY, Koestler DC, Raghavan R, Pei D, Godwin AK. Developing a genetic signature to predict drug response in ovarian cancer. Oncotarget. 2018;9(19):14828–48.PubMedCrossRef
113.
Xiaobo C, Majidi M, Feng M, Shao R, Wang J, Zhao Y, Baladandayuthapani V, Song J, Fang B, Ji L, et al. TUSC2(FUS1)-erlotinib induced vulnerabilities in epidermal growth factor receptor(EGFR) wildtype non-small cell lung cancer(NSCLC) targeted by the repurposed drug auranofin. Sci Rep. 2016;6:35741.PubMedPubMedCentralCrossRef
114.
Eriksson SE, Prast-Nielsen S, Flaberg E, Szekely L, Arner ES. High levels of thioredoxin reductase 1 modulate drug-specific cytotoxic efficacy. Free Radic Biol Med. 2009;47(11):1661–71.PubMedCrossRef
115.
Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 2004;7(2):97–110.PubMedCrossRef
116.
117.
Marmol I, Virumbrales-Munoz M, Quero J, Sanchez-de-Diego C, Fernandez L, Ochoa I, Cerrada E, Yoldi MJR. Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells. J Inorg Biochem. 2017;176:123–33.PubMedCrossRef
118.
Huang KB, Wang FY, Tang XM, Feng HW, Chen ZF, Liu YC, Liu YN, Liang H. Organometallic gold(III) complexes similar to tetrahydroisoquinoline induce ER-stress-mediated apoptosis and pro-death autophagy in A549 cancer cells. J Med Chem. 2018;61(8):3478–90.PubMedCrossRef
119.
Freire Boullosa L, Van Loenhout J, Flieswasser T, De Waele J, Hermans C, Lambrechts H, Cuypers B, Laukens K, Bartholomeus E, Siozopoulou V, et al. Auranofin reveals therapeutic anticancer potential by triggering distinct molecular cell death mechanisms and innate immunity in mutant p53 non-small cell lung cancer. Redox Biol. 2021;42:101949.PubMedPubMedCentralCrossRef
120.
Asadzadeh Z, Safarzadeh E, Safaei S, Baradaran A, Mohammadi A, Hajiasgharzadeh K, Derakhshani A, Argentiero A, Silvestris N, Baradaran B. Current approaches for combination therapy of cancer: the role of immunogenic cell death. Cancers (Basel) 2020;12(4).
121.
Terenzi A, Pirker C, Keppler BK, Berger W. Anticancer metal drugs and immunogenic cell death. J Inorg Biochem. 2016;165:71–9.PubMedCrossRef
122.
Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N, et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology. 2014;3(9):e955691.PubMedPubMedCentralCrossRef
123.
Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer. 2012;12(12):860–75.PubMedCrossRef
124.
Fucikova J, Kepp O, Kasikova L, Petroni G, Yamazaki T, Liu P, Zhao L, Spisek R, Kroemer G, Galluzzi L. Detection of immunogenic cell death and its relevance for cancer therapy. Cell Death Dis. 2020;11(11):1013.PubMedPubMedCentralCrossRef
125.
Zitvogel L, Kepp O, Senovilla L, Menger L, Chaput N, Kroemer G. Immunogenic tumor cell death for optimal anticancer therapy: the calreticulin exposure pathway. Clin Cancer Res. 2010;16(12):3100–4.PubMedCrossRef
126.
Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13(1):54–61.PubMedCrossRef
127.
Martins I, Wang Y, Michaud M, Ma Y, Sukkurwala AQ, Shen S, Kepp O, Metivier D, Galluzzi L, Perfettini JL, et al. Molecular mechanisms of ATP secretion during immunogenic cell death. Cell Death Differ. 2014;21(1):79–91.PubMedCrossRef
128.
Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553(7689):446–54.PubMedCrossRef
129.
Hirsh V. Systemic therapies in metastatic non-small-cell lung cancer with emphasis on targeted therapies: the rational approach. Curr Oncol. 2010;17(2):13–23.PubMedPubMedCentralCrossRef
130.
Martins I, Kepp O, Schlemmer F, Adjemian S, Tailler M, Shen S, Michaud M, Menger L, Gdoura A, Tajeddine N, et al. Restoration of the immunogenicity of cisplatin-induced cancer cell death by endoplasmic reticulum stress. Oncogene. 2011;30(10):1147–58.PubMedCrossRef
131.
Rebe C, Demontoux L, Pilot T, Ghiringhelli F. Platinum derivatives effects on anticancer immune response. Biomolecules. 2019;10(1):13.PubMedCentralCrossRef
132.
Tesniere A, Schlemmer F, Boige V, Kepp O, Martins I, Ghiringhelli F, Aymeric L, Michaud M, Apetoh L, Barault L, et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene. 2010;29(4):482–91.PubMedCrossRef
133.
Bogliolo S, Cassani C, Gardella B, Musacchi V, Babilonti L, Venturini PL, Ferrero S, Spinillo A. Oxaliplatin for the treatment of ovarian cancer. Expert Opin Investig Drugs. 2015;24(9):1275–86.PubMedCrossRef
134.
Kolomeyevskaya NV, Lele SB, Miller A, Riebandt GC, Blum BL, Odunsi KO, Frederick PJ. Oxaliplatin is a safe alternative option for patients with recurrent gynecologic cancers after hypersensitivity reaction to Carboplatin. Int J Gynecol Cancer. 2015;25(1):42–8.PubMedPubMedCentralCrossRef
135.
Grothey A, Goldberg RM. A review of oxaliplatin and its clinical use in colorectal cancer. Expert Opin Pharmacother. 2004;5(10):2159–70.PubMedCrossRef
136.
Raninga PV, Lee AC, Sinha D, Shih YY, Mittal D, Makhale A, Bain AL, Nanayakarra D, Tonissen KF, Kalimutho M, et al. Therapeutic cooperation between auranofin, a thioredoxin reductase inhibitor and anti-PD-L1 antibody for treatment of triple-negative breast cancer. Int J Cancer. 2020;146(1):123–36.PubMedCrossRef
137.
138.
139.
Zhu H, Shan Y, Ge K, Lu J, Kong W, Jia C. Oxaliplatin induces immunogenic cell death in hepatocellular carcinoma cells and synergizes with immune checkpoint blockade therapy. Cell Oncol (Dordr). 2020;43(6):1203–14.CrossRef
140.
141.
Sequeira GR, Sahores A, Dalotto-Moreno T, Perrotta RM, Pataccini G, Vanzulli SI, Polo ML, Radisky DC, Sartorius CA, Novaro V, et al. Enhanced antitumor immunity via endocrine therapy prevents mammary tumor relapse and increases immune checkpoint blockade sensitivity. Cancer Res. 2021;81(5):1375–87.PubMedCrossRef
142.
143.
Goyeneche AA, Seidel EE, Telleria CM. Growth inhibition induced by antiprogestins RU-38486, ORG-31710, and CDB-2914 in ovarian cancer cells involves inhibition of cyclin dependent kinase 2. Invest New Drugs. 2012;30(3):967–80.PubMedCrossRef
144.
Zhang L, Hapon MB, Goyeneche AA, Srinivasan R, Gamarra-Luques CD, Callegari EA, Drappeau DD, Terpstra EJ, Pan B, Knapp JR, et al. Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors. Mol Oncol. 2016;10(7):1099–117.PubMedPubMedCentralCrossRef
145.
146.
Shaveta, Mishra S, Singh P. Hybrid molecules: the privileged scaffolds for various pharmaceuticals. Eur J Med Chem. 2016;124:500–536.
147.
Heuer MA, Pietrusko RG, Morris RW, Scheffler BJ. An analysis of worldwide safety experience with auranofin. J Rheumatol. 1985;12(4):695–9.PubMed
Metadata
Title
The gold complex auranofin: new perspectives for cancer therapy
Authors
Farah H. Abdalbari
Carlos M. Telleria
Publication date
01-12-2021
Publisher
Springer US
Published in
Discover Oncology / Issue 1/2021
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-021-00439-0

Other articles of this Issue 1/2021

Discover Oncology 1/2021 Go to the issue

Review

Wnt/β-catenin signal transduction pathway in prostate cancer and associated drug resistance

Research

RETRACTED ARTICLE: IRE1α-XBP1 but not PERK inhibition exerts anti-tumor activity in osteosarcoma

Research

Nephroblastoma overexpressed protein (NOV) enhances 5-Fu-mediated inhibitory effect of colorectal cancer cell proliferation via JNK/AP-1/caspase-8/caspase-3 pathway

Research

Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice

Research

Routine examination of gallbladder specimens after cholecystectomy: a single-centre analysis of the incidence, clinical and histopathological aspects of incidental gallbladder carcinoma

Research

Endoscopy biopsy is not efficiency enough for diagnosis of mucinous colorectal adenocarcinoma
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits