Reactive oxygen species (ROS) are small molecule metabolites of oxygen that are prone to participate in redox reactions via their high reactivity. Intracellular ROS could be generated in reduced nicotinamide-adenine dinucleotidephosphate (NADPH) oxidase-dependent and/or NADPH oxidase-independent manners. Physiologically, ROS are involved in many signaling cascades that contribute to normal processes. One classical example is that ROS derived from the NADPH oxidase and released in neurotrophils are able to digest invading bacteria. Excessive ROS, however, contribute to pathogenesis of various human diseases including cancer, aging, dimentia and hypertension. As signaling messengers, ROS are able to oxidize many targets such as DNA, proteins and lipids, which may be linked with tumor growth, invasion or metastasis. The present review summarizes recent advances in our comprehensive understanding of ROS-linked signaling pathways in regulation of tumor growth, invasion and metastasis, and focuses on the role of the NADPH oxidase-derived ROS in cancer pathogenesis.
Corresponding Author(s):
WANG Gang,Email:gaw2001@med.cornell.edu
引用本文:
. NADPH oxidase and reactive oxygen species as signaling molecules in carcinogenesis[J]. Frontiers of Medicine in China, 2009, 3(1): 1-7.
Gang WANG. NADPH oxidase and reactive oxygen species as signaling molecules in carcinogenesis. Front Med Chin, 2009, 3(1): 1-7.
Lambeth J D. NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol , 2004, 4(3): 181-189 doi: 10.1038/nri1312
2
Wang G. In: Schwab M, eds. Encyclopedia of Cancer: Reactive oxygen species. 2nd ed. Berlin, Heidelberg , New York: Springer-Verlag. 2008,2559-2562
3
Kanofsky J R. Singlet oxygen production by biological systems. Chem Biol Interact , 1989, 70(1--2): 1-28 doi: 10.1016/0009-2797(89)90059-8
4
Quinn M T, Ammons M C, DeLeo F R. The expanding role of NADPH oxidases in health and disease: no longer just agents of death and destruction. Clin Sci , 2006, 111(1): 1-20 doi: 10.1042/CS20060059
5
Hordijk P L. Regulation of NADPH oxidases: the role of Rac proteins. Circ Res , 2006, 98 (4): 453-463 doi: 10.1161/01.RES.0000204727.46710.5e
6
Dolado I, Swat A, Ajenjo N, De Vita G, Cuadrado A, Nebreda A R. p38α MAP kinase as a sensor of reactive oxygen species in tumorigenesis. Cancer Cell , 2007, 11(2): 191-205 doi: 10.1016/j.ccr.2006.12.013
7
Komatsu D, Kato M, Nakayama J, Miyagawa S, Kamata T. NADPH oxidase 1 plays a critical mediating role in oncogenic Ras-induced vascular endothelial growth factor expression. Oncogene , 2008, 27(34): 4724-4732 doi: 10.1038/onc.2008.102
8
Nakamura H, Nakamura K, Yodoi J. Redox regulation of cellular activation. Ann Rev Immunol , 1997, 15: 351-369 doi: 10.1146/annurev.immunol.15.1.351
9
Valko M, Rhodes C J, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact , 2006, 160(1): 1-40 doi: 10.1016/j.cbi.2005.12.009
10
Wu W S. The signaling mechanism of ROS in tumor progression. Cancer Metast Rev , 2006, 25(4): 695-705 doi: 10.1007/s10555-006-9037-8
11
Xia C, Meng Q, Liu L Z, Rojanasakul Y, Wang X R, Jiang B H. Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res , 2007, 67(22): 10823-10830 doi: 10.1158/0008-5472.CAN-07-0783
12
Brar S S, Corbin Z, Kennedy T P, Hemendinger R, Thornton L, Bommarius B, Arnold R S, Whorton A R, Sturrock A B, Huecksteadt T P, Quinn M T, Krenitsky K, Ardie K G, Lambeth J D, Hoidal J R. NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells. Am J Physiol Cell Physiol , 2003, 285(2): c353-369
13
Brar S S, Kennedy T P, Sturrock A B, Huecksteadt T P, Quinn M T, Whorton A R, Hoidal J R. An NAD(P)H oxidase regulates growth and transcription in melanoma cells. Am J Physiol Cell Physiol , 2002, 282(6): c1212-1224
14
Ohshima H, Tatemichi M. In: Vainio H U, Hietanen E K, eds. Infections, inflammation and cancer: roles of reactive oxygen and nitrogen species. Berlin, Heidelberg , New York: Springer-Verlag. 2003: 211-222
15
Keyer K, Gort A S, Imlay J A. Superoxide and the production of oxidative DNA damage. J Bacteriol , 1995, 177(23): 6782-6790
16
Moore R J, Owens D M, Stamp G, Arnott C, Burke F, East N, Holdsworth H, Turner L, Rollins B, Pasparakis M, Kollias G, Balkwill F. Mice deficient in tumor necrosis factor-alpha are resis tant to skin carcinogenesis. Nat Med , 1999, 5(7): 828-831 doi: 10.1038/10462
17
Pikarsky E, Porat R M, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y. NF-kappa B functions as a tumour promoter in inflammation-associated cancer. Nature , 2004, 431(7007): 461-466 doi: 10.1038/nature02924
18
Ohshima H, Tazawa H, Sylla B S, Sawa T. Prevention of human cancer by modulation of chronic inflammatory processes. Mutat Res , 2005, 591(1--2): 110-122 doi: 10.1016/j.mrfmmm.2005.03.030
19
Kim Y, Lee Y S, Choe J, Lee H, Kim Y M, Jeoung D. CD44-epidermal growth factor receptor interaction mediates hyaluronic acid-promoted cell motility by activating protein kinase C signaling involving Akt, Rac1, Phox, reactive oxygen species, focal adhesion kinase, and MMP-2. J Biol Chem , 2008, 283(33): 22513-22528 doi: 10.1074/jbc.M708319200
20
Ushio-Fukai M, Nakamura Y. Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett , 2008, 266(1): 37-52 doi: 10.1016/j.canlet.2008.02.044
21
Valko M, Leibfritz D, Moncol J, Cronin M T, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol , 2007, 39(1): 44-84 doi: 10.1016/j.biocel.2006.07.001
22
Warzocha K, Ribeiro P, Bienvenu J, Roy P, Charlot C, Rigal D, Coiffier B, Salles G. Genetic polymorphisms in the tumor necrosis factor locus influence non-Hodgkin's lymphoma outcome. Blood , 1998, 91(10): 3574-3581
23
Nishino H, Tokuda H, Satomi Y, Masuda M, Osaka Y, Yogosawa S, Wada S, Mou X Y, Takayasu J, Murakoshi M, Jinnno K, Yano M. Cancer prevention by antioxidants. Biofactors , 2004, 22(1-4): 57-61 doi: 10.1002/biof.5520220110
24
Lee K T, Tsai S M, Wang S N, Lin S K, Wu S H, Chuang S C, Wu S H, Ma H, Tsai L Y. Glutathione status in the blood and tissues of patients with virus-originated hepatocellular carcinoma. Clin Biochem , 2007, 40(15): 1157-1162 doi: 10.1016/j.clinbiochem.2007.06.012
25
Das S, Khan N, Mukherjee S, Bagchi D, Gurusamy N, Swartz H, Das D K. Redox regulation of resveratrol-mediated switching of death signal into survival signal. Free Radic Biol Med , 2008, 44(1): 82-90 doi: 10.1016/j.freeradbiomed.2007.09.008
26
Shankar S, Ganapathy S, Srivastava R K. Green tea polyphenols: biology and therapeutic implications in cancer. Front Biosci , 2007, 12: 4881-4899 doi: 10.2741/2435
27
Tian B, Xu Z, Sun Z, Lin J, Hua Y. Evaluation of the antioxidant effects of carotenoids from Deinococcus radiodurans through targeted mutagenesis, chemiluminescence, and DNA damage analyses. Biochim Biophys Acta , 2007, 1770(6): 902-911
28
Bedard K, Krause K H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev , 2007, 87(1): 245-313 doi: 10.1152/physrev.00044.2005
29
Wang G, Anrather J, Glass M J, Tarsitano M J, Zhou P, Frys K A, Pickel V M, Iadecola C. Nox2, Ca2+ and PKC play a role in angiotensin II-induced free radical production in nucleus tractus solitarius. Hypertension , 2006, 48 (3): 482-489 doi: 10.1161/01.HYP.0000236647.55200.07
30
Wilkinson B L, Landreth G E. The microglial NADPH oxidase complex as a source of oxidative stress in Alzheimer’s disease. J Neuroinflamm , 2006, 3: 30 doi: 10.1186/1742-2094-3-30
31
Tieu K, Ischiropoulos H, Przedborski S. Nitric oxide and reactive oxygen species in Parkinson's disease. IUBMB Life , 2003, 55(6): 329-335 doi: 10.1080/1521654032000114320
