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Implications of NQO1 in cancer therapy

박헌주|오은택
생화학분자생물학회 (Korean Society Of Biochemistry And Molecular Biology)|2015.11|BMB Reports|제48권 제11호|pp. 609-617

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키워드

Cancer therapyCancer preventionNQO1
주제분류화학

초록

NAD(P)H:quinone oxidoreductase (NQO1), an obligatory two-electron reductase, is a ubiquitous cytosolic enzyme that catalyzes the reduction of quinone substrates. The NQO1- mediated two-electron reduction of quinones can be either chemoprotection/detoxification or a chemotherapeutic response, depending on the target quinones. When toxic quinones are reduced by NQO1, they are conjugated with glutathione or glucuronic acid and excreted from the cells. Based on this protective effect of NQO1, the use of dietary compounds to induce the expression of NQO1 has emerged as a promising strategy for cancer prevention. On the other hand, NQO1-mediated two-electron reduction converts certain quinone compounds (such as mitomycin C, E09, RH1 and -lapachone) to cytotoxic agents, leading to cell death. It has been known that NQO1 is expressed at high levels in numerous human cancers, including breast, colon, cervix, lung, and pancreas, as compared with normal tissues. This implies that tumors can be preferentially damaged relative to normal tissue by cytotoxic quinone drugs. Importantly, NQO1 has been shown to stabilize many proteins, including p53 and p33ING1b, by inhibiting their proteasomal degradation. This review will summarize the biological roles of NQO1 in cancer, with emphasis on recent findings and the potential of NQO1 as a therapeutic target for the cancer therapy.

Abstract

NAD(P)H:quinone oxidoreductase (NQO1), an obligatory two-electron reductase, is a ubiquitous cytosolic enzyme that catalyzes the reduction of quinone substrates. The NQO1- mediated two-electron reduction of quinones can be either chemoprotection/detoxification or a chemotherapeutic response, depending on the target quinones. When toxic quinones are reduced by NQO1, they are conjugated with glutathione or glucuronic acid and excreted from the cells. Based on this protective effect of NQO1, the use of dietary compounds to induce the expression of NQO1 has emerged as a promising strategy for cancer prevention. On the other hand, NQO1-mediated two-electron reduction converts certain quinone compounds (such as mitomycin C, E09, RH1 and -lapachone) to cytotoxic agents, leading to cell death. It has been known that NQO1 is expressed at high levels in numerous human cancers, including breast, colon, cervix, lung, and pancreas, as compared with normal tissues. This implies that tumors can be preferentially damaged relative to normal tissue by cytotoxic quinone drugs. Importantly, NQO1 has been shown to stabilize many proteins, including p53 and p33ING1b, by inhibiting their proteasomal degradation. This review will summarize the biological roles of NQO1 in cancer, with emphasis on recent findings and the potential of NQO1 as a therapeutic target for the cancer therapy.

참고문헌 (91)

  1. Terai K, "Cisplatin enhances the anticancer effect of beta-lapachone by upregulating NQO1", Anticancer Drugs, 20, pp.901~909 (2009)
  2. Nioi P, "Contribution of NAD(P)H:quinoneoxidoreductase 1 to protection against carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine zipper and the arylhydrocarbon receptor basic helix-loop-helix transcription factors", Mutat Res, 555, pp.149~171 (2004)
  3. Kaspar JW, "Antioxidant-induced phosphorylation of tyrosine 486 leads to rapid nuclear export of Bach 1 that allows Nrf2 to bind to the antitoxidant response element and activated defensive gene expression", J Biol Chem, 285, pp.153~162 (2010)
  4. Venugopal R, "Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes", Oncogene, 17, pp.3145~3156 (1998)
  5. Ernster L, "Soluble diaphorase in animal tissues", Acta Chem Scand, 12, pp.595~602 (1958)
  6. Schlager JJ, "Cytosilic NAD(P)H:(quinone-acceptor)oxidoreductase in human normal and tumor tissue: effects of cigarette smoking and alchol", Int J Cancer, 45, pp.403~409 (1990)
  7. Peng Q, "The NQO1 Pro187Ser polymorphism and breast cancer susceptibility: evidence from an updated meta-analysis", Diagn Pathol (2014)[DOI]
  8. Cornblatt BS, "Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast", Carcinogenesis, 28, pp.1485~1490 (2007)
  9. Surh YJ, "Cancer chemoprevention with dietary phytochemicals", Nat Rev Cancer, 3, pp.768~780 (2003)
  10. Chen H, "Association of the NAD(P)H:quinone oxidoreducatase 609CT polymorphism with a decreased lung cancer risk", Cancer Res, 59, pp.3045~3048 (1999)
  11. Lin P, "NAD(P)H : quinone oxidoreductase polymorphism and lung cancer in Taiwna", J Toxicol Environ Health, 58, pp.187~197 (1999)
  12. Lewis SJ, "Polymorphisms in the NAD(P)H: quinone oxidoreductase gene and small cell lung cancer risk in a UK population", Lung Cancer, 34, pp.177~183 (2001)
  13. Song SY, "Clinical significance of NQO1 C609T polymorphisms after postoperative radiation therapy in completely resected nonsmall cell lung cancer", Lung Cancer, 68, pp.278~282 (2010)
  14. Hamajima N, "NAD(P)H : quinone oxidoreductase 1(NQO1)C609T polymorphism and the risk of eight cancers for Japanese", Int J Clin Oncol, 7, pp.103~108 (2002)
  15. Menzel HJ, "Association of NQO1 polymorphsim with spontaneous breast cancer in two independent populations", Br J Cancer, 90, pp.1989~1994 (2004)
  16. Lajin B, "The NQO1 polymorphsim C609T (Pro187Ser) and cancer susceptibility: a comprehensive meta-analysis", Br J Cancer, 109, pp.1325~1337 (2013)
  17. Fan Y, "The NQO1C609T polymorphism and hepatocellular carcinoma risk", Tumour Biol, 35, pp.7343~7350 (2014)
  18. Chang Gun Cho, "Association of the GSTP1 and NQO1 Polymorphisms and Head and Neck Squamous Cell Carcinoma Risk", Journal of Korean Medical Science, 21(6), pp.1075~1079 (2006), 대한의학회
  19. Zheng B, "NQO1 C609T polymorphism and colorectal cancer susceptibility: a metaanalysis", Arch Med Sci, 10, pp.651~660 (2014)
  20. Anwar A, "Interaction of the molecular chaperone Hsp70 with human NAD(P)H: quinone oxidoreductase 1", J Biol Chem, 277, pp.14060~14067 (2002)
  21. Traver RD, "NAD(P)H:quinone oxidoreductase gene expression in human colon carcinoma cells: characterization of a mutation which modulates DT-diaphorase activity and mitomycin sensitivity", Cancer Res, 52, pp.797~802 (1992)
  22. Ma Y, "NQO1 overexpression is associated with poor prognosis in squamous cell carcinoma of the uterine cervix", BMC Cancer, 14, pp.414~ (2014)[DOI]
  23. Yang Y, "Clinical implications of high NQO1 expression in breast cancers", J Exp Clin Cancer Res, 33, pp.14~ (2014)[DOI]
  24. Cresteil T, "High levels of expression of the NAD(P)H: quinone oxidoreductase (NQO1) gene in tumor cells compared to normal cells of the same origin", Biochem Pharmacol, 42, pp.1021~1027 (1991)
  25. Siegel D, "Immunohistochemical detection of NAD(P)H: quinone oxidoreductase in human lung and lung tumors", Clin Cancer Res, 4, pp.2065~2070 (1998)
  26. Beall HD, "Nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase (DT-diaphorase) as a target for bioreductive antitumor quinones: quinone cytotoxicity and selectivity in human lung and breast cancer cell lines", Mol Pharmacol, 48, pp.499~504 (1995)
  27. Siegel D, "NAD(P)H:quinone oxidoreductase 1: role as a superoxide scavenger", Mol Pharmacol, 65, pp.1238~1247 (2004)
  28. Winski SL, "Subcellular localization of NAD(P)H:quinone oxidoreducatase 1in human cancer cells", Cancer Res, 62, pp.1420~1424 (2002)
  29. Ross D, "NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms", Chem Biol Interact, 129, pp.77~97 (2000)
  30. Gibson NW, "Relationship between DT-diaphorase mediated metabolism of a series of aziridinyl benzoquinones and DNA damage and cytotoxicity", Mol Pharmacol, 42, pp.531~536 (1992)
  31. Gustafson DL, "Expression of human NQO1 (DT-diaphorase) in Chinese hamster ovary cells: effect on the toxicity of antitumor quinones", Mol Pharmacol, 50, pp.728~735 (1996)
  32. Mikami K, "DT-diaphorase as a critical determinant of sensitivity to mitomycin C in human colon and gastric carcinoma cell lines", Cancer Res, 56, pp.2823~2826 (1996)
  33. Ross D, "Enzymology of bioreductive drug activation", Br J Cancer, 74, pp.1~8 (1996)
  34. Kelland LR, "DT-Diaphorase expression and tumor cell sensitivity to 17-allylamino, 17-demethoxygeldanamycin, an inhibitor of heat shock protein 90", J Natl Cancer Inst, 91, pp.1940~1949 (1999)
  35. Winski SL, "Relationship between NAD(P)H:quinone oxidoreductase 1 (NQO1) levels in a series of stably transfected cell lines and susceptibility to antitumor quinones", Biochem Pharmacol, 61, pp.1509~1516 (2001)
  36. Loadman PM, "Pharmacological approach towards the development of indole quinone bioreductive drugs used on the clinically inactive agent EO9", Br J Pharmacol, 137, pp.701~709 (2002)
  37. Goetz MP, "Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer", J Clin Oncol, 23, pp.1078~1087 (2005)
  38. Choi EK, "Upregulation of NAD(P)H:Quinone Oxidoreductase by radiation potentiates the effect of bioreductive -lapachone on cancer cells", Neoplasia, 9, pp.634~642 (2007)
  39. Park HJ, "Susceptibility of cancer cells to beta-lapachone is enhanced by ionizing radiation", Int J Radiat Oncol Biol Phys, 61, pp.212~219 (2005)
  40. Suzuki M, "Synergistic effects of radiation and beta-lapachone in DU-145 human prostate cancer cells in vitro", Radiat Res, 165, pp.525~531 (2006)
  41. Park HJ, "Heat-induced up-regulation of NAD(P)H: quinone oxidoreductase potentiates anticancer effects of beta-lapachone", Clin Cancer Res, 11, pp.8866~8871 (2005)
  42. Song CW, "Anti-cancer effect of bio-reductive drug beta-lapachon is enhanced by activating NQO1 with heat shock", Int J Hyperthermia, 24, pp.161~169 (2008)
  43. Dinkova-Kostova A, "NAD(P)H : quinone acceptor oxidoreducatase 1(NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector", Arch Biochem Biophys, 501, pp.116~123 (2010)
  44. Asher G, "A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73", Genes Dev, 19, pp.316~321 (2005)
  45. Asher G, "NQO1 stabilizes p53 through a distinct pathway", Proc Natl Acad Sci U S A, 99, pp.3099~3104 (2001)
  46. Anwar A, "Interaction of human NAD(P)H:Quinone Oxidoreductase 1 (NQO1) with the tumor suppressor protein p53 in cells and cell-free systems", J Biol Chem, 278, pp.10368~10373 (2003)
  47. Garate M, "NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of the tumour suppressor p33ING1b", EMBO Rep, 9, pp.576~581 (2008)
  48. Patrick BA, "Stress-induced NQO1controls stability of C", EBP against 20S proteasomal degradation to regulate p63 expression with implications in protection against chemical-induced skin cancer, 2012, pp.31, 4362~4371
  49. Cuendet M, "Quinone reductase induction as a biomarker for cancer chemoprevention", J Nat Prod, 69, pp.460~463 (2006)
  50. Zhu H, "NAD(P)H : quinone oxidoreductase 1 and its potential protective role in cardiovascular diseases and related conditions", Cardiovasc Toxicol, 12, pp.39~45 (2012)
  51. Williams JB, "Rat liver NAD(P)H:quinone reductase", J Biol Chem, 261, pp.5524~5528 (1986)
  52. Jaiswal AK, "Human dioxin-inducible cytosolic NAD(P)H:quinone oxidoreductase", J Biol Chem, 263, pp.13572~13578 (1988)
  53. Ross D, "NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms", Chem Biol Interact, 129, pp.77~97 (2000)
  54. Atia A, "A review of NAD(P)H:quinone oxidoreductase 1 (NQO1); A multifunctional antioxidant enzyme", J Appl Pharm Sci, 4, pp.118~122 (2014)
  55. Nebert DW, "NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: a HuGE review", Genet Med, 4, pp.62~70 (2002)
  56. Lind C, "DT-diaphorase : purification properties and function", Methods Enzymol, 186, pp.287~301 (1990)
  57. Wefers H, "Hepatic low-level chemiluminescence during redox cycling of menadione and the menadione-glutathion conjugate: relation to glutathione and NAD(P)H:quinone reductase (DT-diaphorase) activity", Arch Biochem Biophys, 224, pp.568~578 (1983)
  58. Li R, "The three dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two electron reduction", Proc Natl Acad Sci U S A, 92, pp.8846~8850 (1995)
  59. Talalay P, "Role of nicotinamide quinone oxidoreductase 1 (NQO1) in protection against toxicity of electrophiles and reactive oxygen intermediates", Meth Enzymol, 382, pp.355~364 (2004)
  60. Cenas N, "Structure-activity relationships in two-electron reduction of quinones", Meth Enzymol, 382, pp.258~277 (2004)
  61. Ross D, "Quinone reductases multitasking in the metabolic world", Drug Metabol Rev, 36, pp.639~654 (2004)
  62. Siegel D, "Immunodetection of NAD(P)H:quinone oxidoreductase 1 (NQO1) in human tissues", Free Radical Bio Med, 29, pp.246~253 (2000)
  63. Asher G, "20S proteasomal degradation of ornithine decarboxylase is regulated by NQO1", Mol Cell, 17, pp.645~655 (2005)
  64. Li Y, "Human antioxidant response element mediated regulation of type 1 NAD(P)H: quinone oxidoreductase gene expression", Eur J Biochem, 226, pp.31~39 (1994)
  65. Vasiliou V, "Mouse dioxin-inducible NAD(P)H: menadione oxidoreductase: NMO1cDNA sequence and genetic differences in mRNA levels", Pharmacogenetics, 4, pp.341~348 (1994)
  66. Robertson JA, "NAD(P)H : menadione oxidoreductase. Novel purification of enzyme, cDNA and complete amino acid sequence and gene regulation", J Biol Chem, 261, pp.15794~15799 (1986)
  67. Itoh K, "An Nrf2:small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements", Biochem Biophys Res Commun, 236, pp.313~322 (1997)
  68. Wasserman WW, "Functional antioxidant responsive elements", Proc Natl Acad Sci U S A, 94, pp.5361~5366 (1997)
  69. Li Y, "Mechanism of chemical activation of Nrf2", PLoS One, 7, pp.e35122~ (2012)
  70. Landers JP, "The Ah receptor and the mechanism of dioxin toxicity", Biochem J, 276, pp.273~287 (1991)
  71. Kumaki K, "Genetic differences in induction of cytosol reduced-NAD(P): menadione oxidoreductase and microsomal aryl hydrocarbon hydroxylase in the mouse", J Biol Chem, 252, pp.157~165 (1977)
  72. Radjendirane V, "Antioxidant response element-mediated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)induction of human NAD(P)H:quinone oxidoreductase 1gene expression", Biochem Pharmacol, 58, pp.1649~1655 (1999)
  73. Sporn MB, "The war on cancer", Lancet, 347, pp.1377~1381 (1996)
  74. Kensler TW, "Chemoprevention by inducers of carcinogen detoxication enzymes", Environ. Health Perspect, 105, pp.965~970 (1997)
  75. Fahey JW, "Antioxidant functions of sulforaphane:a potent inducer of Phase II detoxication enzymes", Food Chem Toxicol, 37, pp.973~979 (1999)
  76. Siegel D, "Rapid polyubiquitination and proteasomal degradation of a mutant from of NAD(P)H:quinone oxidoreductase 1", Mol Pharmacol, 59, pp.263~268 (2001)
  77. Rothman N, "Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C T mutation and rapid fractional excretion of chlorzoxazone", Cancer Res, 57, pp.2839~2842 (1997)
  78. Malkinson AM, "Elevated DT-diaphorase activity and messenger RNA content in human non-small cell lung carcinoma: relationship to the response of lung tumor xenografts to mitomycin Cl", Cancer Res, 52, pp.4752~4757 (1992)
  79. Siegel D, "Immunodetection ofNAD(P):quinone oxidoreductase 1 (NQO1) in human tissues", Free Rad Biol Med, 29, pp.246~253 (2000)
  80. Cancer Genome Atlas Research Network(TCGA), "Comprehensive genomic characterization define human colon and rectal cancer", Nature, 487, pp.330~337 (2012)
  81. Siegel D, "NAD(P)H : quinone oxidoreductase 1(NQO1)in the sensitivity and resistance to antitumor quinones", Biochem Pharmacol, 83, pp.1033~1040 (2012)
  82. Begleiter A, "Role of NAD(P)H:(quinone acceptor) oxidoreductase (DT-diaphorase)in activation of mitomycin C under hypoxia", Mol Pharmacol, 41, pp.677~682 (1992)
  83. Dong GZ, "Heat shock increases expression of NAD(P)H:quinone oxidoreductase (NQO1), mediator of beta-lapachone cytotoxicity, by increasing NQO1 gene activity and via Hsp70-mediated stabilization of NQO1 protein", Int J Hypethermia, 25, pp.477~487 (2009)
  84. Park MT, "β-lapachone significantly increases the effect of ionizing radiation to cause mitochondrial apoptosis activation in cancer cells", PLoS One, 6, pp.e25976~ (2011)
  85. Boveris A, "Effect of beta-lapachone on superoxide anion and hydrogen peroxide production in Trypanosoma cruzi", Biochem J, 175, pp.431~439 (1978)
  86. Li LH, "Effects of geldanamycin and its derivatives on RNA-directed DNA polymerase and infectivity of Rauscher leukemia virus", Cancer Treat Rep, 61, pp.815~824 (1977)
  87. Guo W, "Formation of 17-allylamino-demethoxygeldanamycin (17-AAG) hydroquinone by NAD(P)H:-quinone oxidoreductase 1: role of 17-AAG hydroquinone in heat shock protein 90 inhibition", Cancer Res, 65, pp.10006~10015 (2005)
  88. Khong HT, "A phase 2study of ARQ 501 in combination with gemcitabine in adult patients with treatment naïve, unresectable pancreatic adenocarcinoma. ASCO Annual Meeting Proceedings Part I", J Clin Oncol, 25, pp.15017~ (2007)
  89. Blanco E, "Beta-lapachonecontaining PEG-PLA polymer micelles as novel nanotherapeutics against NQO1-overexpressing tumor cells", J Control Release, 122, pp.365~374 (2007)
  90. Dong Y, "Intratumoral delivery of beta-lapachone via polymer implants for prostate cancer therapy", Clin Cancer Res, 15, pp.131~139 (2009)
  91. Park C, "Cyclodextrin-covered gold nanoparticles for targeted delivery of an anti-cancer drug", J Mater Chem, 19, pp.2310~2315 (2009)

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