• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
WU Shiwei, ZHANG Hui, LI Qianbin, HU Gaoyun. Advances in thioredoxin reductase and its inhibitors[J]. Journal of China Pharmaceutical University, 2016, 47(5): 511-520. DOI: 10.11665/j.issn.1000-5048.20160502
Citation: WU Shiwei, ZHANG Hui, LI Qianbin, HU Gaoyun. Advances in thioredoxin reductase and its inhibitors[J]. Journal of China Pharmaceutical University, 2016, 47(5): 511-520. DOI: 10.11665/j.issn.1000-5048.20160502

Advances in thioredoxin reductase and its inhibitors

More Information
  • Thioredoxin reductase(TrxR)is a seleniferous homodimeric flavoenzyme, which is ubiquitously expressed in all cells and plays a crucial role in the redox regulation of numerous celluar signaling pathways involved in cell survival and proliferation. TrxR maintains cellular redox equilibrium. Recent researches have illuminated that TrxR overexpressed in many tumors, is closely associated with the evolution, progression and apoptosis of tumor. TrxR contains a reactive and solvent accessible selenocysteine residue which is located on a flexible C-terminal arm of the protein. This selenocysteine is essentially involved in the catalytic cycle of TrxR and thus represents an attractive binding site for inhibitors. The TrxR inhibitors as novel target-drug in cancer therapy have been extensively studied and elucidated. This article summarized the latest progress in TrxR inhibitors according to the binding capacity of TrxR and substrate.
  • [1]
    Lu J,Holmgren A.The thioredoxin antioxidant system[J].Free Radic Biol Med,2014,66(SI):75-87.
    [2]
    Mahmood DF,Abderrazak A,EI Hadri K,et al.The thioredoxin system as a therapeutic target in human health and disease[J].Antioxid Redox Signal,2013,19(11):1266-1303.
    [3]
    Dal Piaz F,Braca A,Belisario MA,et al.Thioredoxin system modulation by plant and fungal secondary metabolites[J].Curr Med Chem,2010,17(5):479-494.
    [4]
    Zhang BX,Duan DZ,Ge CP,et al.Synthesis of xanthohumol analogues and discovery of potent thioredoxin reductase inhibitor as potential anticancer agent[J].J Med Chem,2015,58(4):1795-1805.
    [5]
    Bindoli A, Rigobello MP. Principles in redox signaling: from chemistry to functional significance[J].Antioxid Redox Signal,2013,18(13):1557-1593.
    [6]
    Zhong L,Arnér ES,Holmgren A.Structure and mechanism of mammalian thioredoxin reductase:the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence[J].Proc Natl Acad Sci U S A,2000,97(11):5854-5859.
    [7]
    Sandalova T, Zhong L, Lindqvist Y, et al. Three-dimensional structure of a mammalian thioredoxin reductase:implications for mechanism and evolution of a selenocysteine-dependent enzyme[J].Proc Acad Sci U S A,2001,98(17):9533-9538.
    [8]
    Urig S,Becker K.On the potential of thioredoxin reductase inhibitors for cancer therapy[J].Semin Cancer Biol,2006,16(6):452-465.
    [9]
    Arnér ES, Holmgren A. The thioredoxin system in cancer[J].Semin Cancer Biol,2006,16(6):420-426.
    [10]
    Yoo MH,Xu XM,Carlson BA,et al.Thioredoxinreductase 1 deficiency reverses tumor phenotype and tumor igenicity of lung carcinoma cells[J].J Biol Chem,2006,281(19):13005-13008.
    [11]
    Koháryová M,Kollárová M.Thioredoxin system - a novel therapeutic target[J].Gen Physiol Biophys,2015,34(3):221-233.
    [12]
    Nguyen P,Awwad RT,Smart DD,et al.Thioredoxin reductase as a novel molecular target for cancer therapy[J].Cancer Lett,2006,236(2):164-174.
    [13]
    Li Y, Zhang LP, Dai F, et al. Hexamethoxylated monocarbonyl analogues of curcumin cause G2/M cell cycle arrest in NCI-H460 cells via michael acceptor- dependent redox intervention[J].J Agric Food Chem,2015,63(35):7731-7742.
    [14]
    Glasauer A,Chandel NS.Targeting antioxidants for cancer therapy[J].Biochem Pharmacol,2014,92(1):90-101.
    [15]
    Liu YP,Duan DZ,Yao J,et al.Dithiaarsanes induce oxidative stress-mediated apoptosis in HL-60 cells by selectively targeting thioredoxin reductase[J].J Med Chem,2014,57(12):5203-5211.
    [16]
    Liu Y,Li Y,Yu S,et al.Recent advances in the development of thioredoxin reductase inhibitors as anticancer agents[J].Curr Drug Targets,2012,13(11):1432-1444.
    [17]
    Králová V,ervinka M,Rudolf E.ROS mediate selenite-induced apoptosis in colon cancer cells[J].Cent Eur J Biol,2010,5(2):166-177.
    [18]
    Mitchell DA, Morton SU, Fernhoff NB, et al. Thioredoxin is required for s-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells[J].Proc Natl Acad Sci U S A,2007,104(28):11609-11614.
    [19]
    Kodela R, Nath N, Chattopadhyay M, et al. Hydrogen sulfide-releasing naproxen suppresses colon cancer cell growth and inhi-bits NF-kappa B signaling[J].Drug Des Devel Ther,2015,9:4873-4882.
    [20]
    Manoharan R, Seong HA, Ha H. Thioredoxin inhibits MPK38-induced ASK1,TGF-beta,and p53 function in a phosphorylation-dependent manner[J].Free Radic Biol Med,2013,63(SI):313-324.
    [21]
    Hellfritsch J,Kirsch J,Schneider M,et al.Knockout of mitochondrial thioredoxin reductase stabilizes prolyl hydroxylase 2 and inhibits tumor growth and tumor-derived angiogenesis[J].Antioxid Redox Signal,2015,22(11):938-950.
    [22]
    Joshi R,Arora S,Kumar A,et al.The competence of 7,8-diacetoxy-4-methylcoumarin and other polyphenolic acetates in mitigating the oxidative stress and their role in angiogenesis[J].Curr Top Med Chem,2015,15(2):179-186.
    [23]
    Gan L, Yang XL, Liu Q, et al. Inhibitory effects of thioredoxin reductaseantisense RNA on the growth of human hepatocellular carcinomacells[J].J Cell Biochem,2005,96(3):653-664.
    [24]
    Saccoccia F,Angelucci F,Boumis G,et al.Thioredoxin reductase and its inhibitors[J].Curr Protein Pept Sci,2014,15(6):621-646.
    [25]
    Sborov DW,Haverkos BM,Harris PJ.Investigational cancer drugs targeting cell metabolism in clinical development[J].Expert Opin Investing Drugs,2015,24(1):79-94.
    [26]
    Wang L,Yang Z,Fu J,et al.Ethaselen:a potent mammalian thioredoxin reductase 1 inhibitor and novel organoselenium anticancer agent[J].Free Radic Biol Med,2012,52(5):898-908.
    [27]
    Cenas N,Nivinskas H,Anusevicius Z,et al.Interactions of quinones with thioredoxin reductase:a challenge to the antioxidant role of the mammalian selenoprotein[J].J Biol Chem,2004,279(4):2583-2592.
    [28]
    Theobald AJ,Caballero I,Coma I,et al.Discovery and biochemical characterization of plasmodium thioredoxin reductase inhibitors from an antimalarial set[J].Biochemistry,2012,51(23):4764-4771.
    [29]
    Cai W,Zhang L,Song Y,et al.Small molecule inhibitors of mammalian thioredoxin reductase[J].Free Radic Biol Med,2012,52(2):257-265.
    [30]
    Meyer A,Oehninger L,Geldmacher Y,et al.Gold(I) N-heterocyclic carbene complexes with naphthalimide ligands as combined thioredoxin reductase inhibitors and DNA intercalators[J].ChemMedChem,2014,9(8):1794-1800.
    [31]
    Serebryanskaya TV,Lyakhov AS,Ivashkevich LS,et al.Gold(I)thiotetrazolates as thioredoxin reductase inhibitors and antiproliferative agents[J].Dalton Trans,2015,44(3):1161-1169.
    [32]
    Mura P,Camalli M,Bindoli A,et al.Activity of rat cytosolic thioredoxin reductase is strongly decreased by trans-[bis(2-amino-5-methylthiazole)tetrachlororuthenate(III)]:first report of relevant thioredoxin reductase inhibition for a ruthenium compound[J].J Med Chem,2007,50(24):5871-5874.
    [33]
    Scolaro C, Bergamo A, Brescacin L, et al. In vitro and in vivo evaluation of ruthenium(II)-arene PTA complexes[J].J Med Chem,2005,48(12):4161-4171.
    [34]
    Casini A,Mastrobuoni G,Ang WH,et al.ESI-MS characterisation of protein adducts of anticancer ruthenium(II)-arene PTA(RAPTA)complexes[J].ChemMedChem,2007,2(5):631-635.
    [35]
    Luo Z,Yu L,Yang F,et al.Ruthenium polypyridyl complexes as inducer of ROS-mediated apoptosis in cancer cells by targeting thioredoxin reductase[J].Metallomics,2014,6(8):1480-1490.
    [36]
    Ferraz KS,Da Silva JG,Costa FM,et al.N(4)-tolyl-2-acetylpyridine thiosemicarbazones and their platinum(II,IV)and gold(III)complexes:cytotoxicity against human glioma cells and studies on the mode of action[J].Biometals,2013,26(5):677-691.
    [37]
    Xie Q,Lan G,Zhou Y,et al.Strategy to enhance the anticancer efficacy of X-ray radiotherapy in melanoma cells by platinum complexes,the role of ROS-mediated signaling pathways[J].Cancer Lett,2014,354(1):58-67.
    [38]
    Fang J,Lu J,Holmgren A.Thioredoxin reductase is irreversibly modified by curcumin:a novel molecular mechanism for its anticancer activity[J].J Biol Chem,2005,280(26):25284-25290.
    [39]
    Singh DV,Agarwal S,Kesharwani RK,et al.3D QSAR and pharmacophore study of curcuminoids and curcumin analogs:interaction with thioredoxin reductase[J].Interdiscip Sci,2013,5(4):286-295.
    [40]
    Wang R,Chen C,Zhang X,et al.Structure-activity relationship and pharmacokinetic studies of 1,5-diheteroarylpenta-1,4-dien-3-ones:a class of promising curcumin-based anticancer agents[J].J Med Chem,2015,58(11):4713-4726.
    [41]
    Lu J,Papp LV,Fang J,et al.Inhibition of Mammalian thioredoxin reductase by some flavonoids:implications for myricetin and quercetin anticancer activity[J].Cancer Res,2006,66(8):4410-4418.
    [42]
    Prietsch RF, Monte LG, da Silva FA, et al. Genistein induces apoptosis and autophagy in human breast MCF-7 cells by modulating the expression of proapoptotic factors and oxidative stress enzymes[J].Mol Cell Biochem,2014,390(1/2):235-242.
    [43]
    Zhu JY, Lou LL, Guo YQ, et al. Natural thioredoxin reductase inhibitors from Jatropha integerrima[J].RSC Adv,2015,5(58):47235-47243.
    [44]
    Liu J,Mu C,Yue W,et al.A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak-independent apoptosis[J].Free Radic Biol Med,2013,63:485-494.
    [45]
    Cotugno R, Gallotta D, Piaz FD, et al. Powerful tumor cell growth-inhibiting activity of a synthetic derivative of atractyligenin:involvement of PI3K/Akt pathway and thioredoxin system[J].Biochim Biophys Acta,2014,1840(3):1135-1144.
    [46]
    Gao FH, Liu F, Wei W, et al. Oridonin induces apoptosis and senescence by increasing hydrogen peroxide and glutathione depletion in colorectal cancer cells[J].Int J Mol Med,2012,29(4):649-655.
    [47]
    Paz MM,Zhang X,Lu J,et al.A new mechanism of action for the anticancer drug mitomycin C:mechanism-based inhibition of thioredoxin reductase[J].Chem Res Toxicol,2012,25(7):1502-1511.
    [48]
    Citta A,Folda A,Bindoli A,et al.Evidence for targeting thioredoxin reductases with ferrocenyl quinone methides.apossible molecular basis for the antiproliferative effect of hydroxyferrocifens on cancer cells[J].J Med Chem,2014,57(21):8849-8859.
    [49]
    Klossowski S, Muchowicz A, Firczuk M, et al. Studies toward novel peptidomimetic inhibitors of thioredoxin-thioredoxin reductase system[J].J Med Chem,2012,55(1):55-67.
    [50]
    Skogastierna C, Johansson M, Parini P, et al. Statins inhibit expression of thioredoxin reductase 1 in rat and human liver and reduce tumour development[J].Biochem Biophys Res Commun,2012,417(3):1046-1051.
    [51]
    Comparsi B,Meinerz DF,Franco JL,et al.Diphenyl ditelluride targets brain selenoproteins in vivo:inhibition of cerebral thioredoxin reductase and glutathione peroxidase in mice after acute exposure[J].Mol Cell Biochem,2012,370(1/2):173-182.
  • Related Articles

    [1]YANG Qian, WANG Xiaojian. Research progress of sphingosine kinase 1 inhibitors[J]. Journal of China Pharmaceutical University, 2021, 52(6): 759-768. DOI: 10.11665/j.issn.1000-5048.20210615
    [2]LI Yin, GU Hongfeng, ZOU Yi, WANG Shuping, XU Yungen. Research progress of mono-(ADP-ribosyl) transferase family and their inhibitors in tumor therapy[J]. Journal of China Pharmaceutical University, 2021, 52(6): 643-652. DOI: 10.11665/j.issn.1000-5048.20210601
    [3]BU Hong, ZHOU Jinpei, ZHANG Huibin. Research progress of mitogen-activated protein kinase interacting kinases inhibitors in tumor immunotherapy[J]. Journal of China Pharmaceutical University, 2021, 52(4): 410-421. DOI: 10.11665/j.issn.1000-5048.20210403
    [4]FENG Yang, XU Xiao, MO Ran. Advances in lymphatic targeted drug delivery system for treatment of tumor metastasis[J]. Journal of China Pharmaceutical University, 2020, 51(4): 425-432. DOI: 10.11665/j.issn.1000-5048.20200406
    [5]TIAN Jiping, ZHANG Jian, ZHOU Jinpei, ZHANG Huibin. Advances in small molecule inhibitors of PD-1/PD-L1 immune checkpoint pathway[J]. Journal of China Pharmaceutical University, 2019, 50(1): 1-10. DOI: 10.11665/j.issn.1000-5048.20190101
    [6]LIU Kejun, ZHANG Zhimin, RAN Ting, CHEN Hongli, LU Tao, CHEN Yadong. Advances in BET bromodomain protein inhibitors[J]. Journal of China Pharmaceutical University, 2015, 46(3): 264-271. DOI: 10.11665/j.issn.1000-5048.20150302
    [7]ZHANG Yuan, CHENG Yulan, ZHOU Jinpei, ZHANG Huibin. Advances on receptor tyrosine kinase inhibitors taking c-Met as anti-tumor target[J]. Journal of China Pharmaceutical University, 2015, 46(1): 16-27. DOI: 10.11665/j.issn.1000-5048.20150102
    [8]LI Chunhong, DU Hongjin, WEN Xiao′an, SUN Hongbin. Advances in inhibitors of MDM2 and MDM4[J]. Journal of China Pharmaceutical University, 2015, 46(1): 1-15. DOI: 10.11665/j.issn.1000-5048.20150101
    [9]DENG Lian-bai, LI Ai-xiu, JIN Yu-rui. Advances in the study on inhibitors of RNase H,a novel anti-HIV drug target[J]. Journal of China Pharmaceutical University, 2011, 42(6): 578-584.
    [10]KONG Kai-lai, LU Shuai, GAO Yi-ping, YANG Pei, TANG Wei-fang, LU Tao. Advances on the study of PLK1 inhibitors as antitumor agents[J]. Journal of China Pharmaceutical University, 2011, 42(1): 9-15.
  • Cited by

    Periodical cited type(2)

    1. 郁莉,蒋颖敏,许磊,朱景宇. 分子对接与分子动力学模拟法探究PI3Kδ/度维利塞(Duvelisib)的选择性结合. 化学研究与应用. 2022(02): 341-348 .
    2. 蔡燕飞,陈蕴,史劲松,金坚. 抗肿瘤药物体外药效学评价结合细胞生物学实验教学促进教研融合. 实验室研究与探索. 2020(08): 192-195 .

    Other cited types(0)

Catalog

    Article views (1426) PDF downloads (4599) Cited by(2)

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return