Recent advances in the development of thioredoxin reductase inhibitors as anticancer agents

Current Drug Targets

Volumn 13, Issue 11, 2012, Pages 1432-1444

  Liu, Yang ^a   Li, Yijing ^a   Yu, Shenghui ^a   Zhao, Guisen ^a  

^a SHANDONG UNIVERSITY   (China)

Author keywords

Cancer; Inhibitor; Thioredoxin reductase; Thioredoxin system

Indexed keywords

5,5' DITHIOBIS(2 NITROBENZOIC ACID); ANTHRANOID DERIVATIVE; ANTINEOPLASTIC AGENT; ANTIOXIDANT; ATORVASTATIN; AURANOFIN; CARBOPLATIN; CINNAMALDEHYDE DERIVATIVE; CISPLATIN; CURCUMIN; FLAVONOID; GOLD COMPLEX; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INDOLE DERIVATIVE; MANSONONE; METAL DERIVATIVE; NATURAL PRODUCTS AND THEIR SYNTHETIC DERIVATIVES; PEPTIDOMIMETIC AGENT; PLATINUM; POLYPHENOL; PORPHYRIN DERIVATIVE; PROTEIN DISULFIDE REDUCTASE (GLUTATHIONE); REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; RUTHENIUM COMPLEX; SELENOCYSTEINE; THIOREDOXIN; THIOREDOXIN REDUCTASE; THIOREDOXIN REDUCTASE INHIBITOR; THIOSEMICARBAZONE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CARCINOGENESIS; CELL FUNCTION; COMPLEX FORMATION; CONCENTRATION RESPONSE; DRUG ACTIVITY; DRUG DESIGN; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME INHIBITION; ENZYME SPECIFICITY; ENZYME SUBSTRATE; GENE TARGETING; HIGH THROUGHPUT SCREENING; HUMAN; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; OXIDATION REDUCTION STATE; REGULATORY MECHANISM; REVIEW; TEA; TUMOR GROWTH; UPREGULATION; WINE;

ANTINEOPLASTIC AGENTS; CELL LINE; ENZYME INHIBITORS; HUMANS; THIOREDOXIN-DISULFIDE REDUCTASE;

EID: 84866915080     PISSN: 13894501     EISSN: 18735592     Source Type: Journal    
DOI: 10.2174/138945012803530224     Document Type: Review

References (101)

1. Myers JM, Myers CR. The effects of hexavalent chromium on thioredoxin reductase and peroxiredoxins in human bronchial epithelial cells. Free Radic Biol Med 2009; 47: 1477-85.
2. Gromer S, Urig S, Becker K. The thioredoxin system-from science to clinic. Med Res Rev 2004; 24: 40-89.
3. Arner ES, Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem / FEBS 2000; 267: 6102-9.
4. Zahedi Avval F, Holmgren A. Molecular mechanisms of thioredoxin and glutaredoxin as hydrogen donors for Mammalian s phase ribonucleotide reductase. J Biol Chem 2009; 284: 8233-40.
5. Holmgren A, Lu J. Thioredoxin and thioredoxin reductase: current research with special reference to human disease. Biochem Biophys Res Commun 2010; 396: 120-4.
6. Heilman JM, Burke TJ, McClain CJ, Watson WH. Transactivation of gene expression by NF-kappaB is dependent on thioredoxin reductase activity. Free Radic Biol Med 2011; 51: 1533-42.
7. Berndt C, Lillig CH, Holmgren A. Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: implications for diseases in the cardiovascular system. Am J Physiol Heart Circ Physiol 2007; 292: H1227-H36.
8. Tonissen KF, Di Trapani G. Thioredoxin system inhibitors as mediators of apoptosis for cancer therapy. Mol Nutr Food Res 2009; 53: 87-103.
9. Turanov AA, Hatfield DL, Gladyshev VN. Characterization of Protein Targets of Mammalian Thioredoxin Reductases. Methods Enzymol 2010; 474: 245-54.
10. Eckenroth B, Harris K, Turanov AA, Gladyshev VN, Raines RT, Hondal RJ. Semisynthesis and characterization of mammalian thioredoxin reductase. Biochemistry 2006; 45: 5158-70.
11. Arnér ESJ. Focus on mammalian thioredoxin reductases-important selenoproteins with versatile functions. Biochim Biophys Acta 2009; 1790: 495-526.
12. Hashemy SI, Ungerstedt JS, Zahedi Avval F, Holmgren A. Motexafin gadolinium, a tumor-selective drug targeting thioredoxin reductase and ribonucleotide reductase. J Biol Chem 2006; 281: 10691-7.
13. Lothrop AP, Ruggles EL, Hondal RJ. No selenium required: reactions catalyzed by mammalian thioredoxin reductase that are independent of a selenocysteine residue. Biochemistry 2009; 48: 6213-23.
14. Kang HJ, Choi SW, Heo DH, Jeong MY, Sung HC, Yun CW. A novel role for thioredoxin reductase in the iron metabolism of S. cerevisiae. Biochem Biophys Res Commun 2008; 371: 63-8.
15. Sun QA, Su D, Novoselov SV, Carlson BA, Hatfield DL, Gladyshev VN. Reaction mechanism and regulation of mammalian thioredoxin/glutathione reductase. Biochemistry 2005; 44: 14528-37.
16. Gasdaska PY, Berggren MM, Berry MJ, Powis G. Cloning, sequencing and functional expression of a novel human thioredoxin reductase. FEBS Lett 1999; 442: 105-11.
17. Rigobello MP, Bindoli A. Mitochondrial Thioredoxin Reductase:: Purification, Inhibitor Studies, and Role in Cell Signaling. Methods Enzymol 2010; 474: 109-22.
18. Lu J, Berndt C, Holmgren A. Metabolism of selenium compounds catalyzed by the mammalian selenoprotein thioredoxin reductase. Biochim Biophys Acta 2009; 1790: 1513-9.
19. Fritz-Wolf K, Urig S, Becker K. The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis. J Mol Biol 2007; 370: 116-27.
20. Papp LV, Lu J, Holmgren A, Khanna KK. From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid Redox Signal 2007; 9: 775-806.
21. Holmgren A. Selenite in cancer therapy: a commentary on "Selenite induces apoptosis in sarcomatoid malignant mesothelioma cells through oxidative stress". Free Radic Biol Med 2006; 41: 862-5.
22. Whanger PD. Selenium and its relationship to cancer: an update. Br J Nutr 2004; 91: 11-28.
23. Bjorkhem-Bergman L, Torndal UB, Eken S, et al. Selenium prevents tumor development in a rat model for chemical carcinogenesis. Carcinogenesis 2005; 26: 125-31.
24. Erkhembayar S, Mollbrink A, Eriksson M, Larsen EH, Eriksson LC. Selenium homeostasis and induction of thioredoxin reductase during long term selenite supplementation in the rat. J Trace Elem Med Biol 2011; 25(4): 254-9.
25. Zeng H, Combs GF, Jr. Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell invasion. J Nutr Biochem 2008; 19: 1-7.
26. Yoo MH, Carlson BA, Tsuji P, Irons R, Gladyshev VN, Hatfield DL. Alteration of thioredoxin reductase 1 levels in elucidating cancer etiology. Methods Enzymol 2010; 474: 255-75.
27. Nakamura H, Masutani H, Yodoi J. Extracellular thioredoxin and thioredoxin-binding protein 2 in control of cancer. Semin Cancer Biol 2006; 16: 444-51.
28. Urig S, Becker K. On the potential of thioredoxin reductase inhibitors for cancer therapy. Semin Cancer Biol 2006; 16: 452-65.
29. Nordberg J, Arner ES. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 2001; 31: 1287-312.
30. Lincoln DT, Ali Emadi EM, Tonissen KF, Clarke FM. The thioredoxin-thioredoxin reductase system: over-expression in human cancer. Anticancer Res 2003; 23: 2425-33.
31. Kim SJ, Miyoshi Y, Taguchi T, et al. High thioredoxin expression is associated with resistance to docetaxel in primary breast cancer. Clin Cancer Res 2005; 11: 8425-30.
32. Arner ES, Holmgren A. The thioredoxin system in cancer. Semin Cancer Biol 2006; 16: 420-6.
33. Jacob C, Giles GI, Giles NM, Sies H. Sulfur and selenium: the role of oxidation state in protein structure and function. Angew Chem Int Ed Engl 2003; 42: 4742-58.
34. Wipf P, Lynch SM, Birmingham A, et al. Natural product based inhibitors of the thioredoxin-thioredoxin reductase system. Org Biomol Chem 2004; 2: 1651-8.
35. Wang L, Yang Z, Fu J, et al. Ethaselen: a potent mammalian thioredoxin reductase 1 inhibitor and novel organoselenium anticancer agent. Free Radic Biol Med 2012; 52: 898-908.
36. Peng Z, Lan L, Zhao F, et al. A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells. J Zhejiang Univ Sci B 2008; 9: 16-21.
37. Zhao F, Yan J, Deng S, et al. A thioredoxin reductase inhibitor induces growth inhibition and apoptosis in five cultured human carcinoma cell lines. Cancer Lett 2006; 236: 46-53.
38. Fu J, Li J, Tan Q, et al. Thioredxin reductase inhibitor ethaselen increases the drug sensitivity of the colon cancer cell line LoVo towards cisplatin via regulation of G1 phase and reversal of G2/M phase arrest. Invest New Drugs 2011; 29: 627-36.
39. Mehta MP, Shapiro WR, Phan SC, et al. Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial. Int J Radiat Oncol Biol Phys2009; 73: 1069-76.
40. Magda D, Miller RA. Motexafin gadolinium: a novel redox active drug for cancer therapy. Semin Cancer Biol 2006; 16: 466-76.
41. Casini A, Hartinger C, Gabbiani C, et al. Gold(III) compounds as anticancer agents: relevance of gold-protein interactions for their mechanism of action. J Inorg Biochem 2008; 102: 564-75.
42. Millet R, Urig S, Jacob J, et al. Synthesis of 5-nitro-2-furancarbohydrazides and their cis-diamminedichloroplatinum complexes as bitopic and irreversible human thioredoxin reductase inhibitors. J Med Chem 2005; 48: 7024-39.
43. 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: 872-81.
44. Tiekink ERT. Phosphinegold (I) thiolates-pharmacological use and potential. Bioinorg Chem Appl 2003; 1: 53.
45. Cox AG, Brown KK, Arner ES, Hampton MB. The thioredoxin reductase inhibitor auranofin triggers apoptosis through a Bax/Bakdependent process that involves peroxiredoxin 3 oxidation. Biochem Pharmacol 2008; 76: 1097-109.
46. Gandin V, Fernandes AP, Rigobello MP, et al. Cancer cell death induced by phosphine gold (I) compounds targeting thioredoxin reductase. Biochem Pharmacol 2010; 79: 90-101.
47. Ronconi L, Marzano C, Zanello P, et al. Gold(III) dithiocarbamate derivatives for the treatment of cancer: solution chemistry, DNA binding, and hemolytic properties. J Med Chem 2006; 49: 1648-57.
48. Talib J, Beck JL, Ralph SF. A mass spectrometric investigation of the binding of gold antiarthritic agents and the metabolite [Au(CN)2]-to human serum albumin. J Biol Inorg Chem 2006; 11: 559-70.
49. Nell MJ, Wagener JM, Zeevaart JR, et al. The anti-tumour properties and biodistribution (as determined by the radiolabeled equivalent) of Au-compounds intended as potential chemotherapeutics. Appl Radiat Isot 2009; 67: 1370-6.
50. Kouroulis KN, Hadjikakou SK, Kourkoumelis N, et al. Synthesis, structural characterization and in vitro cytotoxicity of new Au(III) and Au(I) complexes with thioamides. Dalton Trans 2009: 10446-56.
51. 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: 550-80.
52. Galassi R, Burini A, Ricci S, et al. Synthesis and characterization of azolate gold (I) phosphane complexes as thioredoxin reductase inhibiting antitumor agents. Dalton Trans 2012; 41: 5307-18.
53. Hickey JL, Ruhayel RA, Barnard PJ, Baker MV, Berners-Price SJ, Filipovska A. Mitochondria-targeted chemotherapeutics: the rational design of gold(I) N-heterocyclic carbene complexes that are selectively toxic to cancer cells and target protein selenols in preference to thiols. J Am Chem Soc 2008; 130: 12570-1.
54. Jellicoe MM, Nichols SJ, Callus BA, et al. Bioenergetic differences selectively sensitize tumorigenic liver progenitor cells to a new gold(I) compound. Carcinogenesis 2008; 29: 1124-33.
55. Rubbiani R, Kitanovic I, Alborzinia H, et al. Benzimidazol-2-ylidene gold (I) complexes are thioredoxin reductase inhibitors with multiple antitumor properties. J Med Chem 2010; 53(24): 8608-18.
56. Beraldo H, Gambino D. The wide pharmacological versatility of semicarbazones, thiosemicarba-zones and their metal complexes. Mini Rev Med Chem 2004; 4: 31-9.
57. Lessa JA, Mendes IC, da Silva PR, et al. 2-Acetylpyridine thiosemicarbazones: cytotoxic activity in nanomolar doses against malignant gliomas. Eur J Med Chem 2010; 45: 5671-7.
58. Lessa JA, Guerra JC, de Miranda LF, et al. Gold (I) complexes with thiosemicarbazones: Cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity. J Inorg Biochem 2011; 105(12): 1729-39.
59. Kostova I. Ruthenium complexes as anticancer agents. Curr Med Chem 2006; 13: 1085-107.
60. 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 Med Chem 2007; 50: 5871-4.
61. Scolaro C, Bergamo A, Brescacin L, et al. In vitro and in vivo evaluation of ruthenium(II)-arene PTA complexes. J Med Chem 2005; 48: 4161-71.
62. Casini A, Mastrobuoni G, Ang WH, et al. ESI-MS characterisation of protein adducts of anticancer ruthenium(II)-arene PTA (RAPTA) complexes. ChemMedChem 2007; 2: 631-5.
63. German JB, Walzem RL. The health benefits of wine. Annu Rev Nutr 2000; 20: 561-93.
64. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 2006; 5: 493-506.
65. Lu J, Papp LV, Fang J, Rodriguez-Nieto S, Zhivotovsky B, Holmgren A. Inhibition of Mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity. Cancer Res 2006; 66: 4410-8.
66. Wallenborg K, Vlachos P, Eriksson S, et al. Red wine triggers cell death and thioredoxin reductase inhibition: effects beyond resveratrol and SIRT1. Exp Cell Res 2009; 315: 1360-71.
67. Yang CS, Chung JY, Yang G, Chhabra SK, Lee MJ. Tea and tea polyphenols in cancer prevention. J Nutr 2000; 130: 472S-8S.
68. Lea MA, Xiao Q, Sadhukhan AK, Cottle S, Wang ZY, Yang CS. Inhibitory effects of tea extracts and (-)-epigallocatechin gallate on DNA synthesis and proliferation of hepatoma and erythroleukemia cells. Cancer Lett 1993; 68: 231-6.
69. Shiraki M, Hara Y, Osawa T, Kumon H, Nakayama T, Kawakishi S. Antioxidative and antimutagenic effects of theaflavins from black tea. Mutat Res 1994; 323: 29-34.
70. Du Y, Wu Y, Cao X, et al. Inhibition of mammalian thioredoxin reductase by black tea and its constituents: Implications for anticancer actions. Biochimie 2009; 91: 434-44.
71. Tulp M, Bohlin L. Rediscovery of known natural compounds: nuisance or goldmine? Bioorg Med Chem 2005; 13: 5274-82.
72. Kubin A, Wierrani F, Burner U, Alth G, Grünberger W. Hypericin-the facts about a controversial agent. Curr Pharm Des 2005; 11: 233-53.
73. Sorrentino F, Karioti A, Gratteri P, et al. Hypericins and thioredoxin reductase: Biochemical and docking studies disclose the molecular basis for effective inhibition by naphthodianthrones. Bioorg Med Chem 2011; 19: 631-41.
74. Dinkova-Kostova AT, Massiah MA, Bozak RE, Hicks RJ, Talalay P. Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups. Proc Natl Acad Sci USA 2001; 98: 3404-9.
75. Fang J, Lu J, Holmgren A. Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. J Biol Chem 2005; 280: 25284-90.
76. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: a short review. Life Sci 2006; 78: 2081-7.
77. Gafner S, Lee SK, Cuendet M, et al. Biologic evaluation of curcumin and structural derivatives in cancer chemoprevention model systems. Phytochemistry 2004; 65: 2849-59.
78. Qiu X, Liu Z, Shao WY, et al. Synthesis and evaluation of curcumin analogs as potential thioredoxin reductase inhibitors. Bioorg Med Chem 2008; 16: 8035-41.
79. Wang D, Xia M, Cui Z, Tashiro S, Onodera S, Ikejima T. Cytotoxic effects of mansonone E and F isolated from Ulmus pumila. Biol Pharm Bull 2004; 27: 1025-30.
80. Suh YG, Kim SN, Shin DY, et al. The structure-activity relationships of mansonone F, a potent anti-MRSA sesquiterpenoid quinone: SAR studies on the C6 and C9 analogs. Bioorg Med Chem Lett 2006; 16: 142-5.
81. Huang SL, Luo Y, Huang ZS, et al. Synthesis and Cytotoxicity of 9-Substituted Benzo [de] chromene-7, 8-dione and 5-Benzyl-9-substituted Benzo [de] chromene-7, 8-dione. Synthetic communications 2006; 36: 2667-84.
82. Ka H, Park HJ, Jung HJ, et al. Cinnamaldehyde induces apoptosis by ROS-mediated mitochondrial permeability transition in human promyelocytic leukemia HL-60 cells. Cancer Lett 2003; 196: 143-52.
83. Chew EH, Nagle AA, Zhang Y, et al. Cinnamaldehydes inhibit thioredoxin reductase and induce Nrf2: potential candidates for cancer therapy and chemoprevention. Free Radic Biol Med 2010; 48(1): 98-111.
84. MacDonald JR, Muscoplat CC, Dexter DL, et al. Preclinical antitumor activity of 6-hydroxymethylacylfulvene, a semisynthetic derivative of the mushroom toxin illudin S. Cancer Res 1997; 57: 279-83.
85. Koeppel F, Poindessous V, Lazar V, Raymond E, Sarasin A, Larsen AK. Irofulven cytotoxicity depends on transcriptioncoupled nucleotide excision repair and is correlated with XPG expression in solid tumor cells. Clin Cancer Res 2004; 10: 5604-13.
86. Neels JF, Gong J, Yu X, Sturla SJ. Quantitative correlation of drug bioactivation and deoxyadenosine alkylation by acylfulvene. Chem Res Toxicol 2007; 20: 1513-9.
87. Liu X, Pietsch KE, Sturla SJ. Susceptibility of the Antioxidant Selenoenyzmes Thioredoxin Reductase and Glutathione Peroxidase to Alkylation-Mediated Inhibition by Anticancer Acylfulvenes. Chem Res Toxicol 2011; 24: 726-36.
88. Colucci MA, Reigan P, Siegel D, Chilloux A, Ross D, Moody CJ. Synthesis and evaluation of 3-aryloxymethyl-1,2-dimethylindole-4,7-diones as mechanism-based inhibitors of NAD(P)H:quinone oxidoreductase 1 (NQO1) activity. J Med Chem 2007; 50: 5780-9.
89. Chew EH, Lu J, Bradshaw TD, Holmgren A. Thioredoxin reductase inhibition by antitumor quinols: a quinol pharmacophore effect correlating to antiproliferative activity. FASEB J 2008; 22: 2072-83.
90. Yan C, Shieh B, Reigan P, et al. Potent activity of indolequinones against human pancreatic cancer: identification of thioredoxin reductase as a potential target. Mol Pharmacol 2009; 76: 163-72.
91. Yan C, Siegel D, Newsome J, Chilloux A, Moody CJ, Ross D. Antitumor indolequinones induced apoptosis in human pancreatic cancer cells via inhibition of thioredoxin reductase and activation of redox signaling. Mol Pharmacol 2012; 81: 401-10.
92. Pallis M, Bradshaw TD, Westwell AD, Grundy M, Stevens MF, Russell N. Induction of apoptosis without redox catastrophe by thioredoxin-inhibitory compounds. Biochem Pharmacol 2003; 66: 1695-705.
93. Klossowski S, Muchowicz A, Firczuk M, et al. Studies toward novel peptidomimetic inhibitors of thioredoxin-thioredoxin reductase system. J Med Chem 2012; 55: 55-67.
94. Prast-Nielsen S, Dexheimer TS, Schultz L, et al. Inhibition of thioredoxin reductase 1 by porphyrins and other small molecules identified by a high-throughput screening assay. Free Radic Biol Med 2011; 50: 1114-23.
95. Wilt TJ, Bloomfield HE, MacDonald R, et al. Effectiveness of statin therapy in adults with coronary heart disease. Arch Intern Med 2004; 164: 1427-36.
96. Bjorkhem-Bergman L, Acimovic J, Torndal UB, Parini P, Eriksson LC. Lovastatin prevents carcinogenesis in a rat model for liver cancer. Effects of ubiquinone supplementation. Anticancer Res 2010; 30: 1105-12.
97. Khurana V, Bejjanki HR, Caldito G, Owens MW. Statins reduce the risk of lung cancer in humans: a large case-control study of US veterans. Chest 2007; 131: 1282-8.
98. Skogastierna C, Johansson M, Parini P, et al. Statins inhibit expression of Thioredoxin reductase 1 in rat and human liver and reduce tumour development. Biochem Biophys Res Commun 2012; 417(3): 1046-51.
99. Barnes KM, Evenson JK, Raines AM, Sunde RA. Transcript analysis of the selenoproteome indicates that dietary selenium requirements of rats based on selenium-regulated selenoprotein mRNA levels are uniformly less than those based on glutathione peroxidase activity. J Nutr 2009; 139: 199-206.
100. Carlson BA, Xu XM, Gladyshev VN, Hatfield DL. Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA. J Biol Chem 2005; 280: 5542-8.
101. Moosmann B, Behl C. Selenoprotein synthesis and side-effects of statins. Lancet 2004; 363: 892-4.