Auranofin is a highly effective thioredoxin reductase (TrxR) inhibitor (IC50 = 0.2μM) [1]. Auranofin binds to the selenocysteine residue embedded in the active site of TrxR through gold ions, inhibiting the activity of this key antioxidant enzyme, resulting in decreased intracellular reducing capacity and increased oxidative stress, which in turn activates signaling pathways such as mitochondria and nuclear factor κB, inducing cell apoptosis [2-3]. Auranofin is commonly used to treat rheumatoid arthritis [4].
In A549 cells, Treatment with different concentrations of Auranofin (0-5μM; 24h) inhibited cell proliferation in a dose-dependent manner [5]. In Calu3 and HCC366 cells, treatment with Auranofin (0.5μM; 24h, 48h) induces massive cell death or apoptosis [6]. In NCI-H460 and NCI-H1299 cells, Auranofin (0-5μM; 24h) inhibited cell growth in a dose-dependent manner [7].
In C. difficile infection (CDI) mouse model, Auranofin (0.125mg/kg, 0.25mg/kg, 0.5mg/kg; po; 5d) significantly prevented CDI recurrence [8]. In mice with diet-induced obesity model, Auranofin (1mg/kg; ip; 4 weeks) exerts antidiabetic effects [9]. In MiaPaCa-2 pancreatic tumors mouse model, Auranofin (5mg/kg, 10mg/kg, 15mg/kg; ip; 21d) presents a survival advantage in nude mice with MiaPaCa-2 pancreatic tumors and inhibits metastasis in a dose-dependent fashion [10].
References:
[1]. Davis P. Auranofin. Clinics in Rheumatic Diseases. 1984 Aug 1;10(2):369-383.
[2]. Shen S, Shen J, Luo Z, et al. Molecular mechanisms and clinical implications of the gold drug auranofin. Coordination Chemistry Reviews. 2023 Oct 15; 493: 215323.
[3]. Madeira JM, Gibson DL, Kean WF, et al. The biological activity of auranofin: implications for novel treatment of diseases. Inflammopharmacology. 2012 Dec; 20: 297-306.
[4]. Finkelstein AE, Walz DT, Batista V, et al. Auranofin. New oral gold compound for treatment of rheumatoid arthritis. Annals of the rheumatic diseases. 1976 Jun 1; 35(3): 251-257.
[5]. Cui XY, Park SH, Park WH. Anti-cancer effects of auranofin in human lung cancer cells by increasing intracellular ROS levels and depleting GSH levels. Molecules. 2022 Aug 15; 27(16): 5207.
[6]. Li H, Hu J, Wu S, et al. Auranofin-mediated inhibition of PI3K/AKT/mTOR axis and anticancer activity in non-small cell lung cancer cells. Oncotarget. 2015 Dec 9; 7(3): 3548.
[7]. Cui XY, Park SH, Park WH. Auranofin inhibits the proliferation of lung cancer cells via necrosis and caspase-dependent apoptosis. Oncology Reports. 2020 Dec; 44(6): 2715-2724.
[8]. Abutaleb NS, Seleem MN. Auranofin, at clinically achievable dose, protects mice and prevents recurrence from Clostridioides difficile infection. Scientific reports. 2020 May 7; 10(1): 7701.
[9]. Cox AR, Masschelin PM, Saha PK, et al. The rheumatoid arthritis drug auranofin lowers leptin levels and exerts antidiabetic effects in obese mice. Cell metabolism. 2022 Dec 6; 34(12): 1932-1946.
[10]. Perez MV, Roife D, Dai B, et al. Antineoplastic effects of auranofin in human pancreatic adenocarcinoma preclinical models. Surgery Open Science. 2019 Oct 1; 1(2): 56-63.
Auranofin是一种高效的硫氧还蛋白还原酶（TrxR）抑制剂（IC50 = 0.2μM） [1]。Auranofin通过金离子与TrxR活性位点的硒代半胱氨酸残基结合，抑制这种关键抗氧化酶的活性，导致细胞内还原能力下降、氧化应激增强，进而激活线粒体和核因子κB等信号通路，诱导细胞凋亡 [2-3]。Auranofin常用于治疗类风湿性关节炎 [4]。
在A549细胞中，不同浓度的Auranofin（0-5μM；24h）处理以剂量依赖性方式抑制细胞增殖 [5]。在Calu3和HCC366细胞中，Auranofin（0.5μM；24h，48h）处理可诱导大量细胞死亡或凋亡 [6]。在NCI-H460和NCI-H1299细胞中，Auranofin（0-5μM；24h）以剂量依赖性方式抑制细胞生长 [7]。
在艰难梭菌感染（CDI）小鼠模型中，Auranofin（0.125mg/kg，0.25mg/kg，0.5mg/kg；po；5d）显著预防CDI复发 [8]。在饮食诱导的肥胖小鼠模型中，Auranofin（1mg/kg；ip；4周）具有抗糖尿病作用 [9]。在MiaPaCa-2胰腺肿瘤小鼠模型中，Auranofin（5mg/kg，10mg/kg，15mg/kg；ip；21d）在MiaPaCa-2胰腺肿瘤裸鼠中表现出生存优势，并以剂量依赖性方式抑制肿瘤转移 [10]。