Thioredoxin reductase inhibition by antitumor quinols: A quinol pharmacophore effect correlating to antiproliferative activity

FASEB Journal

Volumn 22, Issue 6, 2008, Pages 2072-2083

  Chew, Eng Hui ^a   Lu, Jun ^a   Bradshaw, Tracey D ^b   Holmgren, Arne ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

Anticancer agents; Antitumor mechanism of action; Michael acceptors; Selenocysteine

Indexed keywords

ANTINEOPLASTIC AGENT; QUINOL DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; SELENOCYSTEINE; THIOREDOXIN; THIOREDOXIN REDUCTASE;

ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOTOXICITY; DRUG ACTIVITY; DRUG MECHANISM; ENZYME INHIBITION; HUMAN; HUMAN CELL; PHARMACOPHORE; PRIORITY JOURNAL; SUBSTITUTION REACTION;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL PROLIFERATION; ENZYME INHIBITORS; HUMANS; HYDROQUINONES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THIOREDOXIN-DISULFIDE REDUCTASE;

MAMMALIA; RATTUS;

EID: 44949114211     PISSN: 08926638     EISSN: None     Source Type: Journal    
DOI: 10.1096/fj.07-101477     Document Type: Article

References (61)

1. Arner, E. S., and Holmgren, A. (2000) Physiological functions of thioredoxin and thioredoxin reductase. Eur. J. Biochem. 267, 6102-6109
2. Gromer, S., Urig, S., and Becker, K. (2004) The thioredoxin system-from science to clinic. Med. Res. Rev. 24, 40-89
3. Lillig, C. H., and Holmgren, A. (2007) Thioredoxin and related molecules-from biology to health and disease. Antioxid. Redox Signal. 9, 25-47
4. Papp, L. V., Lu, J., Holmgren, A., and Khanna, K. K. (2007) From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid. Redox Signal. 9, 775-806
5. Matsui, M., Oshima, M., Oshima, H., Takaku, K., Maruyama, T., Yodoi, J., and Taketo, M. M. (1996) Early embryonic lethality caused by targeted disruption of the mouse thioredoxin gene. Dev. Biol. 178, 179-185
6. Nonn, L., Williams, R. R., Erickson, R. P., and Powis, G. (2003) The absence of mitochondrial thioredoxin 2 causes massive apoptosis, exencephaly, and early embryonic lethality in homozygous mice. Mol. Cell. Biol. 23, 916-922
7. Jakupoglu, C., Przemeck, G. K., Schneider, M., Moreno, S. G., Mayr, N., Hatzopoulos, A. K., de Angelis, M. H., Wurst, W., Bornkamm, G. W., Brielmeier, M., and Conrad, M. (2005) Cytoplasmic thioredoxin reductase is essential for embryogenesis but dispensable for cardiac development. Mol. Cell. Biol. 25, 1980-1988
8. Conrad, M., Jakupoglu, C., Moreno, S. G., Lippl, S., Banjac, A., Schneider, M., Beck, H., Hatzopoulos, A. K., Just, U., Sinowatz, F., Schmahl, W., Chien, K. R., Wurst, W., Bornkamm, G. W., and Brielmeier, M. (2004) Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function. Mol. Cell. Biol. 24, 9414-9423
9. Arner, E. S., and Holmgren, A. (2006) The thioredoxin system in cancer. Semin. Cancer Biol. 16, 420-426
10. Berggren, M., Gallegos, A., Gasdaska, J. R., Gasdaska, P. Y., Warneke, J., and Powis, G. (1996) Thioredoxin and thioredoxin reductase gene expression in human tumors and cell lines, and the effects of serum stimulation and hypoxia. Anticancer Res. 16, 3459-3466
11. Soini, Y., Kahlos, K., Napankangas, U., Kaarteenaho-Wiik, R., Saily, M., Koistinen, P., Paaakko, P., Holmgren, A., and Kinnula, V. L. (2001) Widespread expression of thioredoxin and thioredoxin reductase in non-small cell lung carcinoma. Clin. Cancer Res. 7, 1750-1757
12. Kahlos, K., Soini, Y., Saily, M., Koistinen, P., Kakko, S., Paakko, P., Holmgren, A., and Kinnula, V. L. (2001) Up-regulation of thioredoxin and thioredoxin reductase in human malignant pleural mesothelioma. Int. J. Cancer 95, 198-204
13. Kim, S. J., Miyoshi, Y., Taguchi, T., Tamaki, Y., Nakamura, H., Yodoi, J., Kato, K., and Noguchi, S. (2005) High thioredoxin expression is associated with resistance to docetaxel in primary breast cancer Clin. Cancer Res. 11, 8425-8430
14. Raffel, J., Bhattacharyya, A. K., Gallegos, A., Cui, H., Einspahr, J. G., Alberts, D. S., and Powis, G. (2003) Increased expression of thioredoxin-1 in human colorectal cancer is associated with decreased patient survival. J. Lab. Clin. Med. 142, 46-51
15. Yoo, M. H., Xu, X. M., Carlson, B. A., Gladyshev, V. N., and Hatfield, D. L. (2006) Thioredoxin reductase 1 deficiency reverses tumor phenotype and tumorigenicity of lung carcinoma cells. J. Biol. Chem. 281, 13005-13008
16. Wells, G., Berry, J. M., Bradshaw, T. D., Burger, A. M., Seaton, A., Wang, B., Westwell, A. D., and Stevens, M. F. (2003) 4-Substituted 4-hydroxycyclohexa-2,5-dien-1-ones with selective activities against colon and renal cancer cell lines. J. Med. Chem. 46, 532-541
17. Berry, J. M., Bradshaw, T. D., Fichtner, I., Ren, R., Schwalbe, C. H., Wells, G., Chew, E.-H., Stevens, M. F., and Westwell, A. D. (2005) Quinols as novel therapeutic agents. 2.(1) 4-(1-Arylsulfonylindol-2-yl)-4-hydroxycyclohexa- 2,5-dien-1-ones and related agents as potent and selective antitumor agents. J. Med. Chem. 48, 639-644
18. Lion, C. J., Matthews, C. S., Wells, G., Bradshaw, T. D., Stevens, M. F., and Westwell, A. D. (2006) Antitumour properties of fluorinated benzothiazole-substituted hydroxycyclohexa-2,5-dienones ("quinols"). Bioorg. Med. Chem. Lett. 16, 5005-5008
19. McCarroll, A. J., Bradshaw, T. D., Westwell, A. D., Matthews, C. S., and Stevens, M. F. (2007) Quinols as novel therapeutic agents. 7.1 Synthesis of antitumor 4-]1-(arylsulfonyl-1H-indol-2-yl)]-4-hydroxycyclohexa-2,5-dien-1-ones by Sonogashira reactions. J. Med. Chem. 50, 1707-1710
20. Bradshaw, T. D., Matthews, C. S., Cookson, J., Chew, E.-H., Shah, M., Bailey, K., Monks, A., Harris, E., Westwell, A. D., Wells, G., Laughton, C. A., and Stevens, M. F. (2005) Elucidation of thioredoxin as a molecular target for antitumor quinols. Cancer Res. 65, 3911-3919
21. Urig, S., and Becker, K. (2006) On the potential of thioredoxin reductase inhibitors for cancer therapy. Semin. Cancer Biol. 16, 452-465
22. Chew, E.-H., Matthews, C. S., Zhang, J., McCarroll, A. J., Hagen, T., Stevens, M. F., Westwell, A. D., and Bradshaw, T. D. (2006) Antitumor quinols: role of glutathione in modulating quinol-induced apoptosis and identification of putative cellular protein targets. Biochem. Biophys. Res. Commun. 346, 242-251
23. Arner, E. S., Sarioglu, H., Lottspeich, F., Holmgren, A., and Bock, A. (1999) High-level expression in Escherichia coli of selenocysteine-containing rat thioredoxin reductase utilizing gene fusions with engineered bacterial-type SECIS elements and co-expression with the selA, selB and selC genes. J. Mol. Biol. 292, 1003-1016
24. Ren, X., Bjornstedt, M., Shen, B., Ericson, M. L., and Holmgren, A. (1993) Mutagenesis of structural half-cystine residues in human thioredoxin and effects on the regulation of activity by selenodiglutathione. Biochemistry 32, 9701-9708
25. Holmgren, A., and Bjornstedt, M. (1995) Thioredoxin and thioredoxin reductase. Methods Enzymol. 252, 199-208
26. Luthman, M., and Holmgren, A. (1982) Rat liver thioredoxin and thioredoxin reductase: purification and characterization. Biochemistry 21, 6628-6633
27. Arner, E. S., and Holmgren, A. (2000) Measurement of thioredoxin and thioredoxin reductase. In Current Protocols in Toxicology, Supplement 5 (Maines, M.D., Costa, L.G., Reed, D.J., Sassa, S., and Sipes, I.G., eds) pp. 7.4.1-7.4.14, John Wiley & Sons, Inc., New York
28. Rozell, B., Hansson, H. A., Luthman, M., and Holmgren, A. (1985) Immunohistochemical localization of thioredoxin and thioredoxin reductase in adult rats. Eur. J. Cell Biol. 38, 79-86
29. Boyd, M. R., and Paull, K. D. (1995) Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev. Res. 34, 91-104
30. Tamura, T., and Stadtman, T. C. (1996) A new selenoprotein from human lung adenocarcinoma cells: purification, properties, and thioredoxin reductase activity. Proc. Natl. Acad. Sci. U. S. A. 93, 1006-1011
31. Gladyshev, V. N., Jeang, K. T., and Stadtman, T. C. (1996) Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene. Proc. Natl. Acad. Sci. U. S. A. 93, 6146-6151
32. Zhong, L., Arner, E. S., Ljung, J., Aslund, F., and Holmgren, A. (1998) Rat and calf thioredoxin reductase are homologous to glutathione reductase with a carboxyl-terminal elongation containing a conserved catalytically active penultimate selenocysteine residue. J. Biol. Chem. 273, 8581-8591
33. Gasdaska, P. Y., Gasdaska, J. R., Cochran, S., and Powis, G. (1995) Cloning and sequencing of a human thioredoxin reductase. FEBS Lett. 373, 5-9
34. Sandalova, T., Zhong, L., Lindqvist, Y., Holmgren, A., and Schneider, G. (2001) Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. Proc. Natl. Acad. Sci. U. S. A. 98, 9533-9538
35. Arscott, L. D., Gromer, S., Schirmer, R. H., Becker, K., and Williams, C.H. Jr. (1997) The mechanism of thioredoxin reductase from human placenta is similar to the mechanisms of lipoamide dehydrogenase and glutathione reductase and is distinct from the mechanism of thioredoxin reductase from Escherichia coli. Proc. Natl. Acad. Sci. U. S. A. 94, 3621-3626
36. Stadtman, T. C. (1996) Selenocysteine. Annu. Rev. Biochem. 65, 83-100
37. Gorlatov, S. N., and Stadtman, T. C. (1998) Human thioredoxin reductase from HeLa cells: selective alkylation of selenocysteine in the protein inhibits enzyme activity and reduction with NADPH influences affinity to heparin. Proc. Natl. Acad. Sci. U. S. A. 95, 8520-8525
38. Lee, S. R., Kim, J. R., Kwon, K. S., Yoon, H. W., Levine, R. L., Ginsburg, A., and Rhee, S. G. (1999) Molecular cloning and characterization of a mitochondrial selenocysteine-containing thioredoxin reductase from rat liver. J. Biol. Chem. 274, 4722-4734
39. Lee, S. R., Bar-Noy, S., Kwon, J., Levine, R. L., Stadtman, T. C., and Rhee, S. G. (2000) Mammalian thioredoxin reductase: oxidation of the C-terminal cysteine/selenocysteine active site forms a thioselenide, and replacement of selenium with sulfur markedly reduces catalytic activity. Proc. Natl. Acad. Sci. U. S. A. 97, 2521-2526
40. Williams, C. H., Jr. (1992) Lipoamide dehydrogenase, glutathione reductase, thioredoxin reductase, and mercuric ion reductase - A family of flavoenzyme transhydrogenases. In Chemistry and Biochemistry of Flavoenzymes, Vol. 3 (Muller, F., ed) pp. 121-211, CRC Press, Boca Raton, FL, USA
41. Novoselov, S. V., and Gladyshev, V. N. (2003) Non-animal origin of animal thioredoxin reductases: implications for selenocysteine evolution and evolution of protein function through carboxy-terminal extensions. Protein Sci. 12, 372-378
42. Fritz-Wolf, K., Urig, S., and Becker, K. (2007) The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis. J. Mol. Biol. 370, 116-127
43. Biterova, E. I., Turanov, A. A., Gladyshev, V. N., and Barycki, J. J. (2005) Crystal structures of oxidized and reduced mitochondrial thioredoxin reductase provide molecular details of the reaction mechanism. Proc. Natl. Acad. Sci. U. S. A. 102, 15018-15023
44. Sun, Q. A., Kirnarsky, L., Sherman, S., and Gladyshev, V. N. (2001) Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems. Proc. Natl. Acad. Sci. U. S. A. 98, 3673-3678
45. Gromer, S., Wissing, J., Behne, D., Ashman, K., Schirmer, R. H., Flohe, L., and Becker, K. (1998) A hypothesis on the catalytic mechanism of the selenoenzyme thioredoxin reductase. Biochem. J. 332, 591-592
46. Zhong, L., and Holmgren, A. (2000) Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. J. Biol. Chem. 275, 18121-18128
47. Zhong, L., Arner, E. S., and Holmgren, A. (2000) Structure and mechanism of mammalian thioredoxin reductase: the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence. Proc. Natl. Acad. Sci. U. S. A. 97, 5854-5859
48. Dinkova-Kostova, A. T., Massiah, M. A., Bozak, R. E., Hicks, R. J., and Talalay, P. (2001) Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups. Proc. Natl. Acad. Sci. U. S. A. 98, 3404-3409
49. Cenas, N., Nivinskas, H., Anusevicius, Z., Sarlauskas, J., Lederer, F., and Arner, E. S. (2004) Interactions of quinones with thioredoxin reductase: a challenge to the antioxidant role of the mammalian selenoprotein. J. Biol. Chem. 279, 2583-2592
50. Fang, J., Lu, J., and Holmgren, A. (2005) Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. J. Biol. Chem. 280, 25284-25290
51. Lu, J., Papp, L. V., Fang, J., Rodriguez-Nieto, S., Zhivotovsky, B., and Holmgren, A. (2006) Inhibition of mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity. Cancer Res. 66, 4410-4418
52. Gromer, S., Arscott, L. D., Williams, C. H. Jr., Schirmer, R. H., and Becker, K. (1998) Human placenta thioredoxin reductase. Isolation of the selenoenzyme, steady state kinetics, and inhibition by therapeutic gold compounds. J. Biol. Chem. 273, 20096-20101
53. Becker, K., Herold-Mende, C., Park, J. J., Lowe, G., and Schirmer, R. H. (2001) Human thioredoxin reductase is efficiently inhibited by (2,2′-:6′-,2′-terpyridine)platinum(II) complexes. Possible implications for a novel antitumor strategy. J. Med. Chem. 44, 2784-2792
54. Davis, W. Jr., Ronai, Z., and Tew, K. D. (2001) Cellular thiols and reactive oxygen species in drug-induced apoptosis. J. Pharmacol. Exp. Ther. 296, 1-6
55. Witte, A. B., Anestal, K., Jerremalm, E., Ehrsson, H., and Arner, E. S. (2005) Inhibition of thioredoxin reductase but not of glutathione reductase by the major classes of alkylating and platinum-containing anticancer compounds. Free Radic. Biol. Med. 39, 696-703
56. Wang, X., Zhang, J., and Xu, T. (2007) Cyclophosphamide as a potent inhibitor of tumor thioredoxin reductase in vivo. Toxicol. Appl. Pharmacol. 218, 88-95
57. Hashemy, S. I., Ungerstedt, J. S., Zahedi Avval, F., and Holmgren, A. (2006) Motexafin gadolinium, a tumor-selective drug targeting thioredoxin reductase and ribonucleotide reductase. J. Biol. Chem. 281, 10691-10697
58. Lu, J., Chew, E.-H., Holmgren, A. (2007) Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc. Natl. Acad. Sci. U. S. A. 104, 12288-12293
59. Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono, K., and Ichijo, H. (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J. 17, 2596-2606
60. Anestal, K., and Arner, E. S. (2003) Rapid induction of cell death by selenium-compromised thioredoxin reductase 1 but not by the fully active enzyme containing selenocysteine. J. Biol. Chem. 278, 15966-15972
61. Cassidy, P. B., Edes, K., Nelson, C. C., Parsawar, K., Fitzpatrick, F. A., and Moos, P. J. (2006) Thioredoxin reductase is required for the inactivation of tumor suppressor p53 and for apoptosis induced by endogenous electrophiles. Carcinogenesis 27, 2538-2549