Redox-modulating agents target NOX2-dependent IKKε oncogenic kinase expression and proliferation in human breast cancer cell lines

Redox Biology

Volumn 6, Issue , 2015, Pages 9-18

  Mukawera, Espérance ^a   Chartier, Stefany ^a   Williams, Virginie ^a,b   Pagano, Patrick J ^c   Lapointe, Réjean ^a,d   Grandvaux, Nathalie ^a,b  

^a CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

^b UNIVERSITÉ DE MONTRÉAL   (Canada)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^d Institut du Cancer de Montreal   (Canada)

Author keywords

Breast cancer; Cell growth; IKK ; NADPH oxidase; Tempol; Triphenylmethane dyes

Indexed keywords

BRILLIANT GREEN; CASPASE 3; CASPASE 7; CRYSTAL VIOLET; CYCLIN D1; I KAPPA B KINASE EPSILON; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; TEMPOL; TRIPHENYLMETHANE DERIVATIVE; AMINE OXIDE; CASP3 PROTEIN, HUMAN; CASP7 PROTEIN, HUMAN; CCND1 PROTEIN, HUMAN; CYBB PROTEIN, HUMAN; I KAPPA B KINASE; MEMBRANE PROTEIN; QUATERNARY AMMONIUM DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SMALL INTERFERING RNA; SPIN LABEL; SUPEROXIDE;

ARTICLE; BREAST CANCER CELL LINE; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; ENZYME ACTIVATION; HUMAN; HUMAN CELL; HUMAN TISSUE; OXIDATION REDUCTION STATE; OXIDATIVE STRESS; PRIMARY TUMOR; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; RNA INTERFERENCE; ANTAGONISTS AND INHIBITORS; CELL SURVIVAL; DRUG EFFECTS; FEMALE; GENE EXPRESSION REGULATION; GENETICS; MCF-7 CELL LINE; METABOLISM; OXIDATION REDUCTION REACTION; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

GENTIANA;

CASPASE 3; CASPASE 7; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; CYCLIC N-OXIDES; CYCLIN D1; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENTIAN VIOLET; HUMANS; I-KAPPA B KINASE; MCF-7 CELLS; MEMBRANE GLYCOPROTEINS; NADPH OXIDASE; OXIDATION-REDUCTION; QUATERNARY AMMONIUM COMPOUNDS; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; SPIN LABELS; SUPEROXIDES;

EID: 84936882074     PISSN: 22132317     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.redox.2015.06.010     Document Type: Article

References (63)

1. Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell 2000, 100(1):57-70. http://www.ncbi.nlm.nih.gov/pubmed/10647931, 10.1016/S0092-8674(00)81683-9.
2. Thiery J.P., Sastre-Garau X., Vincent-Salomon B., Sigal-Zafrani X., Pierga J.Y., Decraene C., Meyniel J.P., Gravier E., Asselain B., De Rycke Y., Hupe P., Barillot E., Ajaz S., Faraldo M., Deugnier M.A., Glukhova M., Medina D. Challenges in the stratification of breast tumors for tailored therapies. Bull. Cancer 2006, 93(8):E81-E89. Breast Cancer Group. http://www.ncbi.nlm.nih.gov/pubmed/16935776.
3. Clément J.F., Meloche S., Servant M.J. The IKK-related kinases: from innate immunity to oncogenesis. Cell Res. 2008, 18(9):889-899. http://www.ncbi.nlm.nih.gov/pubmed/19160540, 10.1038/cr.2008.273.
4. Hayden M.S., Ghosh S. Shared principles in NF-kappaB signaling. Cell 2008, 132(3):344-362. http://www.ncbi.nlm.nih.gov/pubmed/18267068, 10.1016/j.cell.2008.01.020.
5. Eddy S.F., Guo S., Demicco E.G., Romieu-Mourez R., Landesman-Bollag E., Seldin D.C., Sonenshein G.E. Inducible IkappaB kinase/IkappaB kinase epsilon expression is induced by CK2 and promotes aberrant nuclear factor-kappaB activation in breast cancer cells. Cancer Res. 2005, 65(24):11375-11383. http://www.ncbi.nlm.nih.gov/pubmed/16357145.
6. Boehm J.S., Zhao J.J., Yao J., Kim S.Y., Firestein R., Dunn I.F., Sjostrom S.K., Garraway L.A., Weremowicz S., Richardson A.L., Greulich H., Stewart C.J., Mulvey L.A., Shen R.R., Ambrogio L., Hirozane-Kishikawa T., Hill D.E., Vidal M., Meyerson M., Grenier J.K., Hinkle G., Root D.E., Roberts T.M., Lander E.S., Polyak K., Hahn W.C. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell 2007, 129(6):1065-1079. http://www.ncbi.nlm.nih.gov/pubmed/17574021.
7. Qin B., Cheng K. Silencing of the IKKepsilon gene by siRNA inhibits invasiveness and growth of breast cancer cells. Breast Cancer Res. 2010, 12(5):R74. http://www.ncbi.nlm.nih.gov/pubmed/20863366, 10.1186/bcr2644.
8. Hutti J.E., Shen R.R., Abbott D.W., Zhou A.Y., Sprott K.M., Asara J.M., Hahn W.C., Cantley L.C. Phosphorylation of the tumor suppressor CYLD by the breast cancer oncogene IKKepsilon promotes cell transformation. Mol. Cells 2009, 34(4):461-472. http://www.ncbi.nlm.nih.gov/pubmed/19481526.
9. Guo J.P., Shu S.K., Esposito N.N., Coppola D., Koomen J.M., Cheng J.Q. IKKepsilon phosphorylation of estrogen receptor alpha ser-167 and contribution to tamoxifen resistance in breast cancer. J. Biol. Chem. 2010, 285(6):3676-3684. http://www.ncbi.nlm.nih.gov/pubmed/19940156.
10. Shen R.R., Zhou A.Y., Kim E., Lim E., Habelhah H., Hahn W.C. IκB kinase ε phosphorylates TRAF2 to promote mammary epithelial cell transformation. Mol. Cell. Biol. 2012, 32(23):4756-4768. http://www.ncbi.nlm.nih.gov/pubmed/23007157.
11. Guo J.P., Tian W., Shu S., Xin Y., Shou C., Cheng J.Q. IKBKE phosphorylation and inhibition of FOXO3a: a mechanism of IKBKE oncogenic function. PLOS One 2013, 8(5):e63636. http://www.ncbi.nlm.nih.gov/pubmed/23691078.
12. Hughes-Davies L., Caldas C., Wishart G.C. Tamoxifen: the drug that came in from the cold. Br. J. Cancer 2009, 101(6):875-878. http://www.ncbi.nlm.nih.gov/pubmed/19672259.
13. Halliwell B., Gutteridge J. Free Radicals in Biology and Medicine 2007, 888. Oxford University Books, Oxford, UK. fourth edition.
14. Brown N.S., Bicknell R. Hypoxia and oxidative stress in breast cancer. oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res. 2001, 3(5):323-327. http://www.ncbi.nlm.nih.gov/pubmed/11597322, 10.1186/bcr315.
15. Dröge W. Free radicals in the physiological control of cell function. Physiol. Rev. 2002, 82(1):47-95. http://www.ncbi.nlm.nih.gov/pubmed/11773609, 10.1152/physrev.00018.2001.
16. Giles G.I. The redox regulation of thiol dependent signaling pathways in cancer. Curr. Pharm. Des. 2006, 12(34):4427-4443. http://www.ncbi.nlm.nih.gov/pubmed/17168752, 10.2174/138161206779010549.
17. Jorgenson T.C., Zhong W., Oberley T.D. Redox imbalance and biochemical changes in cancer. Cancer Res. 2013, 73(20):6118-6123. http://www.ncbi.nlm.nih.gov/pubmed/23878188.
18. Gorrini C., Harris I.S., Mak T.W. Modulation of oxidative stress as an anticancer strategy. Nat. Rev. Drug Discov. 2013, 12(12):931-947. http://www.ncbi.nlm.nih.gov/pubmed/24287781, 10.1038/nrd4002.
19. Curtis C.D., Thorngren D.L., Nardulli A.M. Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues. BMC Cancer 2010, 10:9. http://www.ncbi.nlm.nih.gov/pubmed/20064251, 10.1186/1471-2407-10-9.
20. Martinez-Outschoorn U.E., Balliet R., Lin Z., Whitaker-Menezes D., Birbe R.C., Bombonati A., Pavlides S., Lamb R., Sneddon S., Howell A., Sotgia F., Lisanti M.P. BRCA1 mutations drive oxidative stress and glycolysis in the tumor microenvironment: implications for breast cancer prevention with antioxidant therapies. Cell Cycle 2012, 11(23):4402-4413. http://www.ncbi.nlm.nih.gov/pubmed/23172369.
21. Finkel T. Signal transduction by reactive oxygen species. J. Cell Biol. 2011, 194(1):7-15. http://www.ncbi.nlm.nih.gov/pubmed/21746850, 10.1083/jcb.201102095.
22. Janssen-Heininger Y.M.W., Mossman B.T., Heintz N.H., Forman H.J., Kalyanaraman B., Finkel T., Stamler J.S., Rhee S.G., van der Vliet A. Redox-based regulation of signal transduction: principles, pitfalls, and promises. Free Radic. Biol. Med. 2008, 45(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/18423411.
23. Saeidnia S., Abdollahi M. Antioxidants: friends or foe in prevention or treatment of cancer: the debate of the century. Toxicol. Appl. Pharmacol. 2013, 271(1):49-63. http://www.ncbi.nlm.nih.gov/pubmed/23680455, 10.1016/j.taap.2013.05.004.
24. Schiff R., Reddy P., Ahotupa M., Coronado-Heinsohn E., Grim M., Hilsenbeck S.G., Lawrence R., Deneke S., Herrera R., Chamness G.C., Fuqua S.A., Brown P.H., Osborne C.K. Oxidative stress and AP-1 activity in tamoxifen-resistant breast tumors in vivo. J. Natl. Cancer Inst. 2000, 92(23):1926-1934. http://www.ncbi.nlm.nih.gov/pubmed/11106684.
25. Singh B., Bhat N.K., Bhat H.K. Partial inhibition of estrogen-induced mammary carcinogenesis in rats by tamoxifen: balance between oxidant stress and estrogen responsiveness. PLOS One 2011, 6(9):e25125. http://www.ncbi.nlm.nih.gov/pubmed/21966433, 10.1371/journal.pone.0025125.
26. Weitsman G.E., Weebadda W., Ung K., Murphy L.C. Reactive oxygen species induce phosphorylation of serine 118 and 167 on estrogen receptor alpha. Breast Cancer Res. Treat. 2009, 118(2):269-279. http://www.ncbi.nlm.nih.gov/pubmed/18941890, 10.1007/s10549-008-0221-0.
27. Barbie T.U., Alexe G., Aref A.R., Li S., Zhu Z., Zhang X., Imamura Y., Thai T.C., Huang Y., Bowden M., Herndon J., Cohoon T.J., Fleming T., Tamayo P., Mesirov J.P., Ogino S., Wong K.K., Ellis M.J., Hahn W.C., Barbie D.A., Gillanders W.E. Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth. J. Clin. Invest. 2014, 124(12):5411-5423. http://www.ncbi.nlm.nih.gov/pubmed/25365225.
28. Docampo R., Moreno S.N. The metabolism and mode of action of gentian violet. Drug Metab. Rev. 1990, 22(2-3):161-178. http://www.ncbi.nlm.nih.gov/pubmed/2272286, 10.3109/03602539009041083.
29. Balabanova M., Popova L., Tchipeva R. Dyes in dermatology. Clin. Dermatol. 2003, 21(1):2-6. http://www.ncbi.nlm.nih.gov/pubmed/12609582, 10.1016/S0738-081X(02)00330-9.
30. Perry B.N., Govindarajan B., Bhandarkar S.S., Knaus U.G., Valo M., Sturk C., Carrillo C.O., Sohn A., Cerimele F., Dumont D., Losken A., Williams J., Brown L.F., Tan X., Ioffe E., Yancopoulos G.D., Arbiser J.L. Pharmacologic blockade of angiopoietin-2 is efficacious against model hemangiomas in mice. J. Invest. Dermatol. 2006, 126(10):2316-2322. http://www.ncbi.nlm.nih.gov/pubmed/16741507.
31. Zhang X., Zheng Y., Fried L.E., Du Y., Montano S.J., Sohn A., Lefkove B., Holmgren L., Arbiser J.L., Holmgren A., Lu J. Disruption of the mitochondrial thioredoxin system as a cell death mechanism of cationic triphenylmethanes. Free Radic. Biol. Med. 2011, 50(7):811-820. http://www.ncbi.nlm.nih.gov/pubmed/21215310, 10.1016/j.freeradbiomed.2010.12.036.
32. Arbiser J.L., Bips M., Seidler A., Bonner M.Y., Kovach C. Combination therapy of imiquimod and gentian violet for cutaneous melanoma metastases. J. Am. Acad. Dermatol. 2012, 67(2):e81-e83. http://www.ncbi.nlm.nih.gov/pubmed/22794825, 10.1016/j.jaad.2011.10.028.
33. Wilcox C.S. Effects of tempol and redox-cycling nitroxides in models of oxidative stress. Pharmacol. Ther. 2010, 126(2):119-145. http://www.ncbi.nlm.nih.gov/pubmed/20153367, 10.1016/j.pharmthera.2010.01.003.
34. Batinić-Haberle I., Rebouças J.S., Spasojević I. Superoxide dismutase mimics: chemistry, pharmacology, and therapeutic potential. Antioxid. Redox Signal. 2010, 13(6):877-918. http://www.ncbi.nlm.nih.gov/pubmed/20095865.
35. Fink K., Duval A., Martel A., Soucy-Faulkner A., Grandvaux N. Dual role of NOX2 in respiratory syncytial virus- and Sendai virus-induced activation of NF-kappaB in airway epithelial cells. J. Immunol. 2008, 180(10):6911-6922. http://www.ncbi.nlm.nih.gov/pubmed/18453612, 10.4049/jimmunol.180.10.6911.
36. Zhao H., Kalivendi S., Zhang H., Joseph J., Nithipatikom K., Vásquez-Vivar J., Kalyanaraman B. Superoxide reacts with hydroethidine but forms a fluorescent product that is distinctly different from ethidium: potential implications in intracellular fluorescence detection of superoxide. Free Radic. Biol. Med. 2003, 34(11):1359-1368. http://www.ncbi.nlm.nih.gov/pubmed/12757846.
37. Forget M.A., Turcotte S., Beauseigle D., Godin-Ethier J., Pelletier S., Martin J., Tanguay S., Lapointe R. The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types. Br. J. Cancer 2007, 96(4):646-653. http://www.ncbi.nlm.nih.gov/pubmed/17245340.
38. Dussault A.A., Pouliot M. Rapid and simple comparison of messenger RNA levels using real-time PCR. Biol. Proced. Online 2006, 8:1-10. http://www.ncbi.nlm.nih.gov/pubmed/16446781, 10.1251/bpo114.
39. Fink K., Martin L., Mukawera E., Chartier S., De Deken X., Brochiero E., Miot F., Grandvaux N. IFNβ/TNFα synergism induces a non-canonical STAT2/IRF9-dependent pathway triggering a novel DUOX2 NADPH oxidase-mediated airway antiviral response. Cell Res. 2013, 23(5):673-690. http://www.ncbi.nlm.nih.gov/pubmed/23545780, 10.1038/cr.2013.47.
40. Lundholt B.K., Briand P., Lykkesfeldt A.E. Growth inhibition and growth stimulation by estradiol of estrogen receptor transfected human breast epithelial cell lines involve different pathways. Breast Cancer Res. Treat. 2001, 67(3):199-214. http://www.ncbi.nlm.nih.gov/pubmed/11561766, 10.1023/A:1017977406429.
41. Jänicke R.U., Sprengart M.L., Wati M.R., Porter A.G. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J. Biol. Chem. 1998, 273(16):9357-9360. http://www.ncbi.nlm.nih.gov/pubmed/9545256.
42. Maley A.M., Arbiser J.L. Gentian violet: a 19th century drug re-emerges in the 21st century. Exp. Dermatol. 2013, 22(12):775-780. http://www.ncbi.nlm.nih.gov/pubmed/24118276, 10.1111/exd.12257.
43. Nauseef W.M. Detection of superoxide anion and hydrogen peroxide production by cellular NADPH oxidases. Biochim. Biophys. Acta 2014, 1840(2):757-767. http://www.ncbi.nlm.nih.gov/pubmed/23660153, 10.1016/j.bbagen.2013.04.040.
44. Osborne C.K. Tamoxifen in the treatment of breast cancer. N. Engl. J. Med. 1998, 339(22):1609-1618. http://www.ncbi.nlm.nih.gov/pubmed/9828250, 10.1056/NEJM199811263392207.
45. Romieu-Mourez R., Landesman-Bollag E., Seldin D.C., Traish A.M., Mercurio F., Sonenshein G.E. Roles of IKK kinases and protein kinase CK2 in activation of nuclear factor-kappaB in breast cancer. Cancer Res. 2001, 61(9):3810-3818. http://www.ncbi.nlm.nih.gov/pubmed/11325857.
46. Romieu-Mourez R., Landesman-Bollag E., Seldin D.C., Sonenshein G.E. Protein kinase CK2 promotes aberrant activation of nuclear factor-kappaB, transformed phenotype, and survival of breast cancer cells. Cancer Res. 2002, 62(22):6770-6778. http://www.ncbi.nlm.nih.gov/pubmed/12438279.
47. Péant B., Diallo J.S., Lessard L., Delvoye N., Le Page C., Saad F., Mes-Masson A.M. Regulation of IkappaB kinase epsilon expression by the androgen receptor and the nuclear factor-kappaB transcription factor in prostate cancer. Mol. Cancer Res. 2007, 5(1):87-94. http://www.ncbi.nlm.nih.gov/pubmed/17259348, 10.1158/1541-7786.MCR-06-0144.
48. Guo J.P., Shu S.K., He L., Lee Y.C., Kruk P.A., Grenman S., Nicosia S.V., Mor G., Schell M.J., Coppola D., Cheng J.Q. Deregulation of IKBKE is associated with tumor progression, poor prognosis, and cisplatin resistance in ovarian cancer. Am. J. Pathol. 2009, 175(1):324-333. http://www.ncbi.nlm.nih.gov/pubmed/19497997.
49. Graham K.A., Kulawiec M., Owens K.M., Li X., Desouki M.M., Chandra D., Singh K.K. NADPH oxidase 4 is an oncoprotein localized to mitochondria. Cancer Biol. Ther. 2010, 10(3):223-231. http://www.ncbi.nlm.nih.gov/pubmed/20523116, 10.4161/cbt.10.3.12207.
50. Rao Malla R., Raghu H., Rao J.S. Regulation of NADPH oxidase (Nox2) by lipid rafts in breast carcinoma cells. Int. J. Oncol. 2010, 37(6):1483-1493. http://www.ncbi.nlm.nih.gov/pubmed/21042717.
51. Choi J.A., Lee J.W., Kim H., Kim E.Y., Seo J.M., Ko J., Kim J.H. Pro-survival of estrogen receptor-negative breast cancer cells is regulated by a BLT2-reactive oxygen species-linked signaling pathway. Carcinogenesis 2010, 31(4):543-551. http://www.ncbi.nlm.nih.gov/pubmed/19748928.
52. Desouki M.M., Kulawiec M., Bansal S., Das G.M., Singh K.K. Cross talk between mitochondria and superoxide generating NADPH oxidase in breast and ovarian tumors. Cancer Biol. Ther. 2005, 4(12):1367-1373. http://www.ncbi.nlm.nih.gov/pubmed/16294028, 10.4161/cbt.4.12.2233.
53. Ostrakhovitch E.A., Li S.S. NIP1/DUOXA1 expression in epithelial breast cancer cells: regulation of cell adhesion and actin dynamics. Breast Cancer Res. Treat. 2010, 119(3):773-786. http://www.ncbi.nlm.nih.gov/pubmed/19322654, 10.1007/s10549-009-0372-7.
54. Karlenius T.C., Tonissen K.F. Thioredoxin and Cancer: a role for thioredoxin in all states of tumor oxygenation. Cancers 2010, 2(2):209-232. http://www.ncbi.nlm.nih.gov/pubmed/24281068, 10.3390/cancers2020209.
55. Cha M.K., Suh K.H., Kim I.H. Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma. J. Exp. Clin. Cancer Res. 2009, 28:93. http://www.ncbi.nlm.nih.gov/pubmed/19566940.
56. Gariboldi M.B., Lucchi S., Caserini C., Supino R., Oliva C., Monti E. Antiproliferative effect of the piperidine nitroxide tempol on neoplastic and nonneoplastic mammalian cell lines. Free Radic. Biol. Med. 1998, 24(6):913-923. http://www.ncbi.nlm.nih.gov/pubmed/9607601, 10.1016/S0891-5849(97)00372-9.
57. Constantinou C., Papas K.A., Constantinou A.I. Caspase-independent pathways of programmed cell death: the unraveling of new targets of cancer therapy?. Curr. Cancer Drug Targets. 2009, 9(6):717-728. http://www.ncbi.nlm.nih.gov/pubmed/19754356, 10.2174/156800909789271512.
58. Chu I.M., Hengst L., Slingerland J.M. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat. Rev. Cancer 2008, 8(4):253-267. http://www.ncbi.nlm.nih.gov/pubmed/18354415, 10.1038/nrc2347.
59. Burhans W.C., Heintz N.H. The cell cycle is a redox cycle: linking phase-specific targets to cell fate. Free Radic. Biol. Med. 2009, 47(9):1282-1293. http://www.ncbi.nlm.nih.gov/pubmed/19486941, 10.1016/j.freeradbiomed.2009.05.026.
60. Munson JM, Fried L, Rowson SA, Bonner MY, Karumbaiah L, Diaz B, Courtneidge SA, Knaus UG, Brat DJ, Arbiser JL, Bellamkonda RV Anti-invasive adjuvant therapy with imipramine blue enhances chemotherapeutic efficacy against glioma. Sci. Transl. Med. 2012, 4(127):127ra36. 10.1126/scitranslmed.3003016.
61. Rey F.E., Cifuentes M.E., Kiarash A., Quinn M.T., Pagano P.J. Novel competitive inhibitor of NAD(P)H oxidase assembly attenuates vascular O(2)(-) and systolic blood pressure in mice. Circ. Res. 2001, 89(5):408-414. http://www.ncbi.nlm.nih.gov/pubmed/11532901.
62. Csányi G., Cifuentes-Pagano E., Al Ghouleh I., Ranayhossaini D.J., Egaña L., Lopes L.R., Jackson H.M., Kelley E.E., Pagano P.J. Nox2 B-loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2. Free Radic. Biol. Med. 2011, 51(6):1116-1125. http://www.ncbi.nlm.nih.gov/pubmed/21586323.
63. Cifuentes-Pagano E., Saha J., Csányi G., Ghouleh I.A., Sahoo S., Rodríguez A., Wipf P., Pagano P.J., Skoda E.M. Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors. Medchemcomm 2013, 4(7):1085-1092. http://www.ncbi.nlm.nih.gov/pubmed/24466406.