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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 746432, 10 pages
http://dx.doi.org/10.1155/2013/746432
Review Article

The Involvement of NRF2 in Lung Cancer

Department of Environmental and Occupational Health, University of Colorado Anschutz Medical Campus, Mailstop B119-V20, Room. 3125, 12850 East Montview Boulevard, Aurora, CO 80045, USA

Received 8 January 2013; Revised 20 February 2013; Accepted 26 February 2013

Academic Editor: Hye-Youn Cho

Copyright © 2013 Alison K. Bauer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA Cancer Journal for Clinicians, vol. 61, no. 2, pp. 69–90, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. A. Jemal, R. Siegel, E. Ward et al., “Cancer statistics, 2008,” CA Cancer Journal for Clinicians, vol. 58, no. 2, pp. 71–96, 2008. View at Publisher · View at Google Scholar · View at Scopus
  3. Centers for Disease, C and Prevention, “Current tobacco use and secondhand smoke exposure among women of reproductive age-14 countries, 2008–2010,” MMWR Morbidity and Mortality Weekly Report, vol. 61, no. 43, pp. 877–882, 2012. View at Google Scholar
  4. Y. He, B. Jiang, L. S. Li et al., “Secondhand smoke exposure predicted chronic obstructive pulmonary disease and other tobacco related mortality in a 17-years cohort study in China,” Chest, vol. 142, no. 4, pp. 909–918, 2012. View at Google Scholar
  5. D. Schottenfeld, “Etiology and epidemiology of lung cancer,” in Lung Cancer—Principles and Practice, H. I. Pass, Ed., pp. 3–24, Lippincott Williams and Wilkins, Philadelphia, Pa, USA, 2005. View at Google Scholar
  6. Y. E. Miller, “Pathogenesis of lung cancer: 100 Year report,” American Journal of Respiratory Cell and Molecular Biology, vol. 33, no. 3, pp. 216–223, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. R. S. Herbst, J. V. Heymach, and S. M. Lippman, “Molecular origins of cancer: lung cancer,” The New England Journal of Medicine, vol. 359, no. 13, pp. 1367–1380, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. K. Taguchi, H. Motohashi, and M. Yamamoto, “Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution,” Genes to Cells, vol. 16, no. 2, pp. 123–140, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. H. Y. Cho and S. R. Kleeberger, “Nrf2 protects against airway disorders,” Toxicology and Applied Pharmacology, vol. 244, no. 1, pp. 43–56, 2010. View at Google Scholar
  10. B. Rotblat, G. Melino, and R. A. Knight, “Nrf2 and p53: januses in cancer?” Oncotarget, vol. 3, no. 11, pp. 1272–1283, 2012. View at Google Scholar
  11. J. H. Lee, T. O. Khor, L. Shu et al., “Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and progression,” Pharmacology and Therapeutics, vol. 137, no. 2, pp. 153–171, 2013. View at Google Scholar
  12. M. K. Kwak and T. W. Kensler, “Targeting Nrf2 signaling for cancer chemoprevention,” Toxicology and Applied Pharmacology, vol. 244, no. 1, pp. 66–76, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. M. B. Sporn and K. T. Liby, “Nrf2 and cancer: the good, the bad and the importance of context,” Nature Reviews Cancer, vol. 12, no. 8, pp. 564–571, 2012. View at Google Scholar
  14. A. K. Jaiswal, “Nrf2 signaling in coordinated activation of antioxidant gene expression,” Free Radical Biology and Medicine, vol. 36, no. 10, pp. 1199–1207, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. E. Bobrovnikova-Marjon, C. Grigoriadou, D. Pytel et al., “PERK promotes cancer cell proliferation and tumor growth by limiting oxidative DNA damage,” Oncogene, vol. 29, no. 27, pp. 3881–3895, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. S. B. Cullinan, D. Zhang, M. Hannink, E. Arvisais, R. J. Kaufman, and J. A. Diehl, “Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival,” Molecular and Cellular Biology, vol. 23, no. 20, pp. 7198–7209, 2003. View at Publisher · View at Google Scholar · View at Scopus
  17. J. D. Hayes, M. McMahon, S. Chowdhry, and A. T. Dinkova-Kostova, “Cancer chemoprevention mechanisms mediated through the keap1-Nrf2 pathway,” Antioxidants and Redox Signaling, vol. 13, no. 11, pp. 1713–1748, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. R. Hu, C. L. L. Saw, R. Yu, and A. N. T. Kong, “Regulation of NF-E2-related factor 2 signaling for cancer chemoprevention: antioxidant coupled with antiinflammatory,” Antioxidants and Redox Signaling, vol. 13, no. 11, pp. 1679–1698, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. R. M. Perera and N. Bardeesy, “Cancer: when antioxidants are bad,” Nature, vol. 475, no. 7354, pp. 43–44, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. N. McCarthy, “Tumorigenesis: oncogene detox programme,” Nature Reviews Cancer, vol. 11, no. 9, pp. 622–623, 2011. View at Google Scholar
  21. T. Rangasamy, C. Y. Cho, R. K. Thimmulappa et al., “Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice,” Journal of Clinical Investigation, vol. 114, no. 9, pp. 1248–1259, 2004. View at Publisher · View at Google Scholar · View at Scopus
  22. H. Y. Cho, S. P. Reddy, A. DeBiase, M. Yamamoto, and S. R. Kleeberger, “Gene expression profiling of Nrf2-mediated protection against oxidative injury,” Free Radical Biology and Medicine, vol. 38, no. 3, pp. 325–343, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. H. Y. Cho, F. Imani, L. Miller-DeGraff et al., “Antiviral activity of Nrf2 in a murine model of respiratory syncytial virus disease,” American Journal of Respiratory and Critical Care Medicine, vol. 179, no. 2, pp. 138–150, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. R. Kim, J. E. Oh, M. S. Kim et al., “Oncogenic Nrf2 mutations in squamous cell carcinomas of oesophagus and skin,” Journal of Pathology, vol. 220, no. 4, pp. 446–451, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. P. A. Konstantinopoulos, D. Spentzos, E. Fountzilas et al., “Keap1 mutations and Nrf2 pathway activation in epithelial ovarian cancer,” Cancer Research, vol. 71, no. 15, pp. 5081–5089, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. K. Iida, K. Itoh, Y. Kumagai et al., “Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis,” Cancer Research, vol. 64, no. 18, pp. 6424–6431, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. T. O. Khor, M. T. Huang, K. H. Kwon, J. Y. Chan, B. S. Reddy, and A. N. Kong, “Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium-induced colitis,” Cancer Research, vol. 66, no. 24, pp. 11580–11584, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. T. O. Khor, M. T. Huang, A. Prawan et al., “Increased susceptibility of Nrf2 knockout mice to colitis-associated colorectal cancer,” Cancer Prevention Research, vol. 1, no. 3, pp. 187–191, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. C. Xu, M. T. Huang, G. Shen et al., “Inhibition of 7,12-dimethylbenz(a)anthracene-induced skin tumorigenesis in C57BL/6 mice by sulforaphane is mediated by nuclear factor E2-related factor 2,” Cancer Research, vol. 66, no. 16, pp. 8293–8296, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. C. D. Klassen, Ed., Toxicology: The Basic Science of Poisons, McGraw-Hill, 6th edition, 2001.
  31. H. P. Witschi, “Selected examples of free-radical-mediated lung injury,” in Free Radical Toxicology, K. B. Wallace, Ed., pp. 274–294, Taylor and Francis, New York, NY, USA, 1997. View at Google Scholar
  32. N. R. Hackett, A. Heguy, B. G. Harvey et al., “Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers,” American Journal of Respiratory Cell and Molecular Biology, vol. 29, no. 3, part I, pp. 331–343, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. D. Hanahan and R. A. Weinberg, “The hallmarks of cancer,” Cell, vol. 100, no. 1, pp. 57–70, 2000. View at Google Scholar · View at Scopus
  34. S.-H. Park, J.-H. Kim, G. Y. Chi et al., “Induction of apoptosis and autophagy by sodium selenite in A549 human lung carcinoma cells through generation of reactive oxygen species,” Toxicology Letters, vol. 212, no. 3, pp. 252–261, 2012. View at Publisher · View at Google Scholar
  35. V. Malec, O. R. Gottschald, S. Li, F. Rose, W. Seeger, and J. Hänze, “HIF-1α signaling is augmented during intermittent hypoxia by induction of the Nrf2 pathway in NOX1-expressing adenocarcinoma A549 cells,” Free Radical Biology and Medicine, vol. 48, no. 12, pp. 1626–1635, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. D. Siegel and D. Ross, “Immunodetection of NAD(P)H:quinone oxidoreductase 1 (NQO1) in human tissues,” Free Radical Biology and Medicine, vol. 29, no. 3-4, pp. 246–253, 2000. View at Publisher · View at Google Scholar · View at Scopus
  37. A. K. Bauer, H.-Y. Cho, L. Miller-DeGraff et al., “Targeted deletion of Nrf2 reduces urethane-induced lung tumor development in mice,” PLoS One, vol. 6, no. 10, Article ID e26590, 2011. View at Google Scholar
  38. Y. Hu, Y. Ju, D. Lin et al., “Mutation of the Nrf2 gene in non-small cell lung cancer,” Molecular Biology Reports, vol. 39, no. 4, pp. 4743–4747, 2012. View at Publisher · View at Google Scholar
  39. H. Motohashi and M. Yakamoto, “Carcinogenesis and transcriptional regulation through Maf recognition elements,” Cancer Science, vol. 98, no. 2, pp. 135–139, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. L. M. Solis, C. Behrens, W. Dong et al., “Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinicopathologic features,” Clinical Cancer Research, vol. 16, no. 14, pp. 3743–3753, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. J. D. Hayes and M. McMahon, “Nrf2 and KEAP1 mutations: permanent activation of an adaptive response in cancer,” Trends in Biochemical Sciences, vol. 34, no. 4, pp. 176–188, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. T. Muller and A. Hengstermann, “Nrf2: friend and foe in preventing cigarette smoking-dependent lung disease,” Chemical Research in Toxicology, vol. 25, no. 9, pp. 1805–1824, 2012. View at Google Scholar
  43. T. Shibata, T. Ohta, K. I. Tong et al., “Cancer related mutations in Nrf2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 36, pp. 13568–13573, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. K. Itoh, K. Igarashi, N. Hayashi, M. Nishizawa, and M. Yamamoto, “Cloning and characterization of a novel erythroid cell-derived CNC family transcription factor heterodimerizing with the small Maf family proteins,” Molecular and Cellular Biology, vol. 15, no. 8, pp. 4184–4193, 1995. View at Google Scholar · View at Scopus
  45. H. Motohashi, T. O'Connor, F. Katsuoka, J. D. Engel, and M. Yamamoto, “Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors,” Gene, vol. 294, no. 1-2, pp. 1–12, 2002. View at Publisher · View at Google Scholar · View at Scopus
  46. K. Itoh, N. Wakabayashi, Y. Katoh et al., “Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain,” Genes and Development, vol. 13, no. 1, pp. 76–86, 1999. View at Google Scholar · View at Scopus
  47. H. Sasaki, M. Shitara, K. Yokota et al., “Increased Nrf2 gene (NFE2L2) copy number correlates with mutations in lung squamous cell carcinomas,” Molecular Medicine Reports, vol. 6, no. 2, pp. 391–394, 2012. View at Google Scholar
  48. L. Hu, W. Miao, M. Loignon, M. Kandouz, and G. Batist, “Putative chemopreventive molecules can increase Nrf2-regulated cell defense in some human cancer cell lines, resulting in resistance to common cytotoxic therapies,” Cancer Chemotherapy and Pharmacology, vol. 66, no. 3, pp. 467–474, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. A. Singh, S. Boldin-Adamsky, R. K. Thimmulappa et al., “RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapy,” Cancer Research, vol. 68, no. 19, pp. 7975–7984, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. H. R. Kim, S. Kim, E. J. Kim et al., “Suppression of Nrf2-driven heme oxygenase-1 enhances the chemosensitivity of lung cancer A549 cells toward cisplatin,” Lung Cancer, vol. 60, no. 1, pp. 47–56, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. S. Homma, Y. Ishii, Y. Morishima et al., “Nrf2 enhances cell proliferation and resistance to anticancer drugs in human lung cancer,” Clinical Cancer Research, vol. 15, no. 10, pp. 3423–3432, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. B. Ebert, M. Kisiela, P. Malátková, Y. El-Hawari, and E. Maser, “Regulation of human carbonyl reductase 3 (CBR3; SDR21C2) expression by Nrf2 in cultured cancer cells,” Biochemistry, vol. 49, no. 39, pp. 8499–8511, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. C. M. Mahaffey, N. C. Mahaffey, W. Holland et al., “Aberrant regulation of the MRP3 gene in non-small cell lung carcinoma,” Journal of Thoracic Oncology, vol. 7, no. 1, pp. 34–39, 2012. View at Publisher · View at Google Scholar
  54. H. Yang, W. Wang, Y. Zhang et al., “The role of NF-E2-related factor 2 in predicting chemoresistance and prognosis in advanced non-small-cell lung cancer,” Clinical Lung Cancer, vol. 12, no. 3, pp. 166–171, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. D. Inoue, T. Suzuki, Y. Mitsuishi et al., “Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma,” Cancer Science, vol. 103, no. 4, pp. 760–766, 2012. View at Publisher · View at Google Scholar
  56. T. Ohta, K. Iijima, M. Miyamoto et al., “Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth,” Cancer Research, vol. 68, no. 5, pp. 1303–1309, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. Q. K. Li, A. Singh, S. Biswal, F. Askin, and E. Gabrielson, “KEAP1 gene mutations and Nrf2 activation are common in pulmonary papillary adenocarcinoma,” Journal of Human Genetics, vol. 56, no. 3, pp. 230–234, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. A. Singh, V. Misra, R. K. Thimmulappa et al., “Dysfunctional KEAP1-Nrf2 interaction in non-small-cell lung cancer,” PLoS Medicine, vol. 3, no. 10, article e420, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. C. M. Mahaffey, H. Zhang, A. Rinna, W. Holland, P. C. Mack, and H. J. Forman, “Multidrug-resistant protein-3 gene regulation by the transcription factor Nrf2 in human bronchial epithelial and non-small-cell lung carcinoma,” Free Radical Biology and Medicine, vol. 46, no. 12, pp. 1650–1657, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. S. L. Gelhaus, O. Giladb, W.-T. Hwang et al., “Multidrug resistance protein (MRP) 4 attenuates benzo[a]pyrene-mediated DNA-adduct formation in human bronchoalveolar H358 cells,” Toxicology Letters, vol. 209, no. 1, pp. 58–66, 2012. View at Publisher · View at Google Scholar
  61. M. Zhang, A. Mathur, Y. Zhang et al., “Mithramycin represses basal and cigarette smoke-induced expression of ABCG2 and inhibits stem cell signaling in lung and esophageal cancer cells,” Cancer Research, vol. 72, no. 16, pp. 4178–4192, 2012. View at Google Scholar
  62. A. Singh, H. Wu, P. Zhang, C. Happel, J. Ma, and S. Biswal, “Expression of ABCG2 (BCRP) is regulated by Nrf2 in cancer cells that confers side population and chemoresistance phenotype,” Molecular Cancer Therapeutics, vol. 9, no. 8, pp. 2365–2376, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. L. A. Muscarella, P. Parrella, V. D'Alessandro et al., “Frequent epigenetics inactivation of KEAP1 gene in non-small cell lung cancer,” Epigenetics, vol. 6, no. 6, pp. 710–719, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. P. Zhang, A. Singh, S. Yegnasubramanian et al., “Loss of kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth,” Molecular Cancer Therapeutics, vol. 9, no. 2, pp. 336–346, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. L. Zhan, H. Zhangb, Q. Zhang et al., “Regulatory role of KEAP1 and Nrf2 in PPARgamma expression and chemoresistance in human non-small-cell lung carcinoma cells,” Free Radical Biology and Medicine, vol. 53, no. 4, pp. 758–768, 2012. View at Publisher · View at Google Scholar
  66. S. K. Niture and A. K. Jaiswal, “INrf2 (Keap1) targets Bcl-2 degradation and controls cellular apoptosis,” Cell Death and Differentiation, vol. 18, no. 3, pp. 439–451, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. S. K. Niture and A. K. Jaiswal, “Nrf2 protein up-regulates antiapoptotic protein Bcl-2 and prevents cellular apoptosis,” The Journal of Biological Chemistry, vol. 287, no. 13, pp. 9873–9886, 2012. View at Google Scholar
  68. A. D. Panani and C. Roussos, “Cytogenetic and molecular aspects of lung cancer,” Cancer Letters, vol. 239, no. 1, pp. 1–9, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. Cancer Genome Atlas Research Network, “Comprehensive genomic characterization of squamous cell lung cancers,” Nature, vol. 489, no. 7417, pp. 519–525, 2012. View at Google Scholar
  70. T. Shibata, S. Saito, A. Kokubu, T. Suzuki, M. Yamamoto, and S. Hirohashi, “Global downstream pathway analysis reveals a dependence of oncogenic NF-E2—related factor 2 mutation on the mTOR growth signaling pathway,” Cancer Research, vol. 70, no. 22, pp. 9095–9105, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. T. Suzuki, J. Maher, and M. Yamamoto, “Select heterozygous Keap1 mutations have a dominant-negative effect on wild-type Keap1 in vivo,” Cancer Research, vol. 71, no. 5, pp. 1700–1709, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. A. M. Malkinson, “The genetic basis of susceptibility to lung tumors in mice,” Toxicology, vol. 54, no. 3, pp. 241–271, 1989. View at Google Scholar · View at Scopus
  73. A. M. Malkinson, “Primary lung tumors in mice: an experimentally manipulable model of human adenocarcinoma,” Cancer Research, vol. 52, supplement 9, pp. 2670s–2676s, 1992. View at Google Scholar · View at Scopus
  74. A. M. Malkinson, “Molecular comparison of human and mouse pulmonary adenocarcinomas,” Experimental Lung Research, vol. 24, no. 4, pp. 541–555, 1998. View at Google Scholar · View at Scopus
  75. B. Zimmerli and J. Schlatter, “Ethyl carbamate: analytical methodology, occurrence, formation, biological activity and risk assessment,” Mutation Research, vol. 259, no. 3-4, pp. 325–350, 1991. View at Google Scholar · View at Scopus
  76. S. Shibutani, M. Takeshita, and A. P. Grollman, “Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG,” Nature, vol. 349, no. 6308, pp. 431–434, 1991. View at Publisher · View at Google Scholar · View at Scopus
  77. G. M. Denicola, F. A. Karreth, T. J. Humpton et al., “Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis,” Nature, vol. 475, no. 7354, pp. 106–110, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. H. Satoh, T. Moriguchi, K. Taguchi et al., “Nrf2-deficiency creates a responsive microenvironment for metastasis to the lung,” Carcinogenesis, vol. 31, no. 10, pp. 1833–1843, 2010. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Nagaraj, K. Gupta, V. Pisarev et al., “Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer,” Nature Medicine, vol. 13, no. 7, pp. 828–835, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. C. D. Mills, “Macrophage arginine metabolism to ornithine/urea or nitric oxide/citrulline: a life or death issue,” Critical Reviews in Immunology, vol. 21, no. 5, pp. 399–425, 2001. View at Google Scholar · View at Scopus
  81. S. L. Slocum and T. W. Kensler, “Nrf2: control of sensitivity to carcinogens,” Archives of Toxicology, vol. 85, no. 4, pp. 273–284, 2011. View at Google Scholar
  82. T. W. Kensler and N. Wakabayashi, “Nrf2: friend or foe for chemoprevention?” Carcinogenesis, vol. 31, no. 1, Article ID bgp231, pp. 90–99, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. L. Shu, K. L. Cheung, T. O. Khor, C. Chen, and A. N. Kong, “Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis,” Cancer and Metastasis Reviews, vol. 29, no. 3, pp. 483–502, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. R. Patel and G. Maru, “Polymeric black tea polyphenols induce phase II enzymes via Nrf2 in mouse liver and lungs,” Free Radical Biology and Medicine, vol. 44, no. 11, pp. 1897–1911, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. S. J. London, J. M. Yuan, F. L. Chung et al., “Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China,” The Lancet, vol. 356, no. 9231, pp. 724–729, 2000. View at Google Scholar · View at Scopus
  86. P. Talalay and J. W. Fahey, “Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism,” Journal of Nutrition, vol. 131, supplement 11, pp. 3027S–3033S, 2001. View at Google Scholar · View at Scopus
  87. J. W. Fahey and P. Talalay, “Antioxidant functions of sulforaphane: a potent inducer of phase II detoxication enzymes,” Food and Chemical Toxicology, vol. 37, no. 9-10, pp. 973–979, 1999. View at Publisher · View at Google Scholar · View at Scopus
  88. J. D. Hayes, J. U. Flanagan, and I. R. Jowsey, “Glutathione transferases,” Annual Review of Pharmacology and Toxicology, vol. 45, pp. 51–88, 2005. View at Publisher · View at Google Scholar · View at Scopus
  89. H. Y. Cho, S. P. Reddy, and S. R. Kleeberger, “Nrf2 defends the lung from oxidative stress,” Antioxidants and Redox Signaling, vol. 8, no. 1-2, pp. 76–87, 2006. View at Publisher · View at Google Scholar · View at Scopus
  90. R. Garg, S. Gupta, and G. B. Maru, “Dietary curcumin modulates transcriptional regulators of phase I and phase II enzymes in benzo[a]pyrene-treated mice: mechanism of its anti-initiating action,” Carcinogenesis, vol. 29, no. 5, pp. 1022–1032, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. S. Biswas and I. Rahman, “Modulation of steroid activity in chronic inflammation: a novel anti-inflammatory role for curcumin,” Molecular Nutrition and Food Research, vol. 52, no. 9, pp. 987–994, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. A. K. Bauer and E. A. Rondini, “Review Paper: The role of inflammation in mouse pulmonary neoplasia,” Veterinary Pathology, vol. 46, no. 3, pp. 369–390, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. A. M. Malkinson, “Role of inflammation in mouse lung tumorigenesis: a review,” Experimental Lung Research, vol. 31, no. 1, pp. 57–82, 2005. View at Publisher · View at Google Scholar · View at Scopus
  94. D. Schottenfeld and J. Beebe-Dimmer, “Chronic inflammation: a common and important factor in the pathogenesis of neoplasia,” CA Cancer Journal for Clinicians, vol. 56, no. 2, pp. 69–83, 2006. View at Publisher · View at Google Scholar · View at Scopus
  95. M. Kerns, D. DePianto, M. Yamamoto, and P. A. Coulombe, “Differential modulation of keratin expression by sulforaphane occurs via Nrf2-dependent and -independent pathways in skin epithelia,” Molecular Biology of the Cell, vol. 21, no. 23, pp. 4068–4075, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. D. Kalpana Deepa Priya, R. Gayathri, and D. Sakthisekaran, “Role of sulforaphane in the anti-initiating mechanism of lung carcinogenesis in vivo by modulating the metabolic activation and detoxification of benzo(a)pyrene,” Biomedicine and Pharmacotherapy, vol. 65, no. 1, pp. 9–16, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. H. M. Leinonen et al., “Oxidative stress-regulated lentiviral TK/GCV gene therapy for lung cancer treatment,” Cancer Research, vol. 72, no. 23, pp. 6227–6235, 2012. View at Google Scholar
  98. C. P. Guise, M. R. Abbattista, R. S. Singleton et al., “The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3,” Cancer Research, vol. 70, no. 4, pp. 1573–1584, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. B. Padmanabhan, K. I. Tong, T. Ohta et al., “Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer,” Molecular Cell, vol. 21, no. 5, pp. 689–700, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. A. Singh, M. Bodas, N. Wakabayashi, F. Bunz, and S. Biswal, “Gain of Nrf2 function in non-small-cell lung cancer cells confers radioresistance,” Antioxidants and Redox Signaling, vol. 13, no. 11, pp. 1627–1637, 2010. View at Publisher · View at Google Scholar · View at Scopus
  101. E. L. Travis, G. Rachakonda, X. Zhou et al., “Nrf2 deficiency reduces life span of mice administered thoracic irradiation,” Free Radical Biology and Medicine, vol. 51, no. 6, pp. 1175–1183, 2011. View at Publisher · View at Google Scholar
  102. S. Lee, M.-J. Lim, M.-H. Kim et al., “An effective strategy for increasing the radiosensitivity of Human lung Cancer cells by blocking Nrf2-dependent antioxidant responses,” Free Radical Biology and Medicine, vol. 53, no. 4, pp. 807–816, 2012. View at Publisher · View at Google Scholar
  103. D. Ren, N. F. Villeneuve, T. Jiang et al., “Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 4, pp. 1433–1438, 2011. View at Publisher · View at Google Scholar · View at Scopus
  104. Z. Weaver, S. Difilippantonio, J. Carretero et al., “Temporal molecular and biological assessment of an erlotinib-resistant lung adenocarcinoma model reveals markers of tumor progression and treatment response,” Cancer Research, vol. 72, no. 22, pp. 5921–5933, 2012. View at Publisher · View at Google Scholar