| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Cancer Research, Vol 4, Issue 9 2065-2070, Copyright © 1998 by American Association for Cancer Research
ARTICLES |
D Siegel, WA Franklin and D Ross
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA. david.siegel@uchsc.edu
NAD(P)H:quinone oxidoreductase (NQO1) is a flavoenzyme that catalyzes the two-electron reduction of quinones and related compounds. With the use of biochemical assays, NQO1 has been shown to be overexpressed in many types of cancer, including non-small cell lung cancer (NSCLC). NQO1 can bioactivate antitumor quinones such as mitomycin C, and new quinone-based drugs are currently being developed to target this enzyme in tumors such as NSCLC. Because there is no information on the cell-specific expression of NQO1 in lung, the purpose of this study was to examine the expression of NQO1 in human NSCLC, small cell lung cancer, carcinoid lung tumors, and normal lung using immunohistochemistry. A high level of NQO1 protein expression was detected by immunohistochemistry in NSCLC (adenocarcinoma, squamous cell carcinoma, and bronchoalveolar carcinoma), but no NQO1 protein could be detected in small cell lung cancer or carcinoid lung tumors. In addition, NQO1 protein expression was examined by immunohistochemistry in normal lung tissue. A high level of NQO1 protein expression was detected by immunohistochemistry in normal lung respiratory epithelium, with the highest levels of expression observed in ciliated columnar epithelial cells. Significant amounts of NQO1 protein were also detected in the vascular endothelium and adipocytes. These data demonstrate that NQO1 is overexpressed in NSCLC. Cells in normal lung also contain marked NQO1 protein and may be damaged by drugs activated by NQO1. These data validate NSCLC as a target for NQO1-directed agents and suggest that the potential for lung toxicity be considered in the preclinical development of quinone-based antitumor drugs.
This article has been cited by other articles:
|
|
 |
|
  M. Volpato, N. Abou-Zeid, R. W. Tanner, L. T. Glassbrook, J. Taylor, I. Stratford, P. M. Loadman, M. Jaffar, and R. M. Phillips Chemical synthesis and biological evaluation of a NAD(P)H:quinone oxidoreductase-1 targeted tripartite quinone drug delivery system Mol. Cancer Ther., December 1, 2007; 6(12): 3122 - 3130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Ahn, X. Gong, G. Sethi, M. M. Chaturvedi, A. K. Jaiswal, and B. B. Aggarwal Deficiency of NRH:Quinone Oxidoreductase 2 Differentially Regulates TNF Signaling in Keratinocytes: Up-regulation of Apoptosis Correlates with Down-regulation of Cell Survival Kinases Cancer Res., October 15, 2007; 67(20): 10004 - 10011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Bentle, K. E. Reinicke, Y. Dong, E. A. Bey, and D. A. Boothman Nonhomologous End Joining Is Essential for Cellular Resistance to the Novel Antitumor Agent, {beta}-Lapachone Cancer Res., July 15, 2007; 67(14): 6936 - 6945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Bey, M. S. Bentle, K. E. Reinicke, Y. Dong, C.-R. Yang, L. Girard, J. D. Minna, W. G. Bornmann, J. Gao, and D. A. Boothman An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by beta-lapachone PNAS, July 10, 2007; 104(28): 11832 - 11837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Palming, K. Sjoholm, M. Jernas, T. C. Lystig, A. Gummesson, S. Romeo, L. Lonn, M. Lonn, B. Carlsson, and L. M. S. Carlsson The Expression of NAD(P)H:Quinone Oxidoreductase 1 Is High in Human Adipose Tissue, Reduced by Weight Loss, and Correlates with Adiposity, Insulin Sensitivity, and Markers of Liver Dysfunction J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2346 - 2352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Bentle, K. E. Reinicke, E. A. Bey, D. R. Spitz, and D. A. Boothman Calcium-dependent Modulation of Poly(ADP-ribose) Polymerase-1 Alters Cellular Metabolism and DNA Repair J. Biol. Chem., November 3, 2006; 281(44): 33684 - 33696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Guo, P. Reigan, D. Siegel, J. Zirrolli, D. Gustafson, and D. Ross The Bioreduction of a Series of Benzoquinone Ansamycins by NAD(P)H:Quinone Oxidoreductase 1 to More Potent Heat Shock Protein 90 Inhibitors, the Hydroquinone Ansamycins Mol. Pharmacol., October 1, 2006; 70(4): 1194 - 1203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Merker, S. H. Audi, R. D. Bongard, B. J. Lindemer, and G. S. Krenz Influence of pulmonary arterial endothelial cells on quinone redox status: effect of hyperoxia-induced NAD(P)H:quinone oxidoreductase 1 Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L607 - L619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Park, E. K. Choi, J. Choi, K.-J. Ahn, E. J. Kim, I.-M. Ji, Y. H. Kook, S.-D. Ahn, B. Williams, R. Griffin, et al. Heat-Induced Up-Regulation of NAD(P)H:Quinone Oxidoreductase Potentiates Anticancer Effects of {beta}-Lapachone Clin. Cancer Res., December 15, 2005; 11(24): 8866 - 8871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Guo, P. Reigan, D. Siegel, J. Zirrolli, D. Gustafson, and D. Ross 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., November 1, 2005; 65(21): 10006 - 10015. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Audi, R. D. Bongard, G. S. Krenz, D. A. Rickaby, S. T. Haworth, J. Eisenhauer, D. L. Roerig, and M. P. Merker Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs Am J Physiol Lung Cell Mol Physiol, November 1, 2005; 289(5): L788 - L797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Kim and A. E. Nel The Role of Phase II Antioxidant Enzymes in Protecting Memory T Cells from Spontaneous Apoptosis in Young and Old Mice J. Immunol., September 1, 2005; 175(5): 2948 - 2959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.H. Bock, A.S. Wenzlaff, M.L. Cote, S.J. Land, and A.G. Schwartz NQO1 T allele associated with decreased risk of later age at diagnosis lung cancer among never smokers: results from a population-based study Carcinogenesis, February 1, 2005; 26(2): 381 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Siegel, D. L. Gustafson, D. L. Dehn, J. Y. Han, P. Boonchoong, L. J. Berliner, and D. Ross NAD(P)H:Quinone Oxidoreductase 1: Role as a Superoxide Scavenger Mol. Pharmacol., May 1, 2004; 65(5): 1238 - 1247. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. L. Gustafson, D. Siegel, J. C. Rastatter, A. L. Merz, J. C. Parpal, J. K. Kepa, D. Ross, and M. E. Long Kinetics of NAD(P)H:Quinone Oxidoreductase I (NQO1) Inhibition by Mitomycin C in Vitro and in Vivo J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 1079 - 1086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, W. A. Schulz, Y. Li, R. Wang, R. Zotz, D. Wen, D. Siegel, D. Ross, H. E. Gabbert, and M. Sarbia Association of NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism with esophageal squamous cell carcinoma in a German Caucasian and a northern Chinese population Carcinogenesis, May 1, 2003; 24(5): 905 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Zappa, T. Ward, E. Pedrinis, J. Butler, and A. McGown NAD(P)H:Quinone Oxidoreductase 1 Expression in Kidney Podocytes J. Histochem. Cytochem., March 1, 2003; 51(3): 297 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sunaga, T. Kohno, N. Yanagitani, H. Sugimura, H. Kunitoh, T. Tamura, Y. Takei, S. Tsuchiya, R. Saito, and J. Yokota Contribution of the NQO1 and GSTT1 Polymorphisms to Lung Adenocarcinoma Susceptibility Cancer Epidemiol. Biomarkers Prev., August 1, 2002; 11(8): 730 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Anwar, D. Siegel, J. K. Kepa, and D. Ross Interaction of the Molecular Chaperone Hsp70 with Human NAD(P)H:Quinone Oxidoreductase 1 J. Biol. Chem., April 12, 2002; 277(16): 14060 - 14067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Strassburg, C. P. Strassburg, M. P. Manns, and R. H. Tukey Differential Gene Expression of NAD(P)H:Quinone Oxidoreductase and NRH:Quinone Oxidoreductase in Human Hepatocellular and Biliary Tissue Mol. Pharmacol., February 1, 2002; 61(2): 320 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Zappa, T. Ward, J. Butler, E. Pedrinis, and A. McGown Overexpression of NAD(P)H:quinone oxidoreductase 1 in Human Reproductive System J. Histochem. Cytochem., September 1, 2001; 49(9): 1187 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. BERGAMASCHI, G. DE PALMA, P. MOZZONI, S. VANNI, M. V. VETTORI, F. BROECKAERT, A. BERNARD, and A. MUTTI Polymorphism of Quinone-metabolizing Enzymes and Susceptibility to Ozone-induced Acute Effects Am. J. Respir. Crit. Care Med., May 1, 2001; 163(6): 1426 - 1431. [Abstract] [Full Text]
|
|
|
|
 |
|
 L. P. Schelonka, D. Siegel, M. W. Wilson, A. Meininger, and D. Ross Immunohistochemical Localization of NQO1 in Epithelial Dysplasia and Neoplasia and in Donor Eyes Invest. Ophthalmol. Vis. Sci., June 1, 2000; 41(7): 1617 - 1622. [Abstract] [Full Text]
|
|
|
|
|
|
J. J. Pink, S. M. Planchon, C. Tagliarino, M. E. Varnes, D. Siegel, and D. A. Boothman NAD(P)H:Quinone Oxidoreductase Activity Is the Principal Determinant of beta -Lapachone Cytotoxicity J. Biol. Chem., February 25, 2000; 275(8): 5416 - 5424. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
