Nitric oxide and cancer: a review

World Journal of Surgical Oncology

Vaishali Joshi²  Amol R Gadbail¹  Sachin Bagde³  Minal Chaudhary¹  Sheetal Korde Choudhari² 

[1] Department of Oral Pathology & Microbiology, Sharad Pawar Dental College, DMIMS, Sawangi(M), Wardha, Maharashatra, 442 004, India;Department of Oral Pathology & Microbiology, Yerala Dental College and Hospital, Institutional Area, Sector 4, Kharghar, Navi Mumbai, Maharashtra, 410 210, India;Department of Oral Surgery, Yerala Dental College and Hospital, Institutional Area, Sector 4, Kharghar, Mumbai, Maharashtra, 410 210, India

关键词: Nitric oxide synthase;    Nitric oxide;    Human papillomavirus;    H. Pylori;    Lung cancer, Head and Neck cancer;    Gastric cancer;    Breast cancer;   

Others  :  823955
DOI  :  10.1186/1477-7819-11-118

 received in 2013-01-08, accepted in 2013-05-12,  发布年份 2013

【 摘 要 】

Nitric oxide (NO), is a ubiquitous, water soluble, free radical gas, which plays key role in various physiological as well as pathological processes. Over past decades, NO has emerged as a molecule of interest in carcinogenesis and tumor growth progression. However, there is considerable controversy and confusion in understanding its role in cancer biology. It is said to have both tumoricidal as well as tumor promoting effects which depend on its timing, location, and concentration. NO has been suggested to modulate different cancer-related events including angiogenesis, apoptosis, cell cycle, invasion, and metastasis. On the other hand, it is also emerging as a potential anti-oncogenic agent. Strategies for manipulating in vivo production and exogenous delivery of this molecule for therapeutic gain are being investigated. However, further validation and experimental/clinical trials are required for development of novel strategies based on NO for cancer treatment and prevention. This review discusses the range of actions of NO in cancer by performing an online MEDLINE search using relevant search terms and a review of the literature. Various mechanisms by which NO acts in different cancers such as breast, cervical, gastric,colorectal, and head and neck cancers are addressed. It also offers an insight into the dichotomous nature of NO and discusses its novel therapeutic applications for cancer prevention and treatment.

【 授权许可】

   
2013 Korde Choudhari et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G: Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 1987, 84:9265-9269.
• [2]Palmer RMJ, Ferrige AG, Moncada S: Nitric oxide release accounts for the biological activity of endothelial-derived relaxing factor. Nature 1987, 327:524-526.
• [3]Thomson LL, Lawton FG, Knowles RG, Basley JE, Riversomoreno V, Moncada S: NO synthase activity in human gynecological cancer. Cancer Res 1994, 54:1352-1354.
• [4]Taysi S, Uslu C, Akcay F, Sutbeyaz MY: MDA and nitric oxide in the plasma of patients with advanced laryngeal cancer. Surg Today 2003, 33(9):651-654.
• [5]Cabs CS, Brenman JE, Aldape KD, Bredt DS, Isrnael MA: Expression of NOS in human central nervous system tumors. Cancer Res 1995, 55:727-730.
• [6]Reveneau S, Arnould L, Jolimoy G, Hilpert S, Lejeune P, Saint-Giorgio V, Belichard C, Jeannin JF: Nitric oxide synthase in human breast cancer is associated with tumor grade, proliferation rate, and expression of progesterone receptor. Lab Invest 1999, 79:1215-1225.
• [7]Prazma J, Pertrusz P, Mims W, Ball SS, Weissler MC: Immunohistochemical characterization of NOS activity in squamous cell carcinoma of head and neck. Otolaryngol Head Neck Surg 1995, 113:541-549.
• [8]Ying L, Hofseth LJ: An emerging role for endothelial nitric oxide synthase in chronic inflammation and cancer. Cancer Res 2007, 67:1407-1410.
• [9]Shang ZJ, Li JR, Li ZB: Effects of exogenous nitric oxide on oral squamous cell carcinoma: an in vitro study. J Oral Maxillofac Surg 2002, 60(8):905-910.
• [10]Harada K, Supriatno , Kawaguchi S, Tomitaro O, Yoshida H, Sato M: Overexpression of iNOS gene suppresses the tumorigenicity and metastasis of oral cancer cells. In Vivo 2004, 18(4):449-455.
• [11]Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: physiology, pathology, and pharmacology. Pharmacol Rev 1991, 43:109-142.
• [12]Ambs S, Merriam WG, Ogunfusika MO, Bennett WP, Ishibe N, Hussain SP, Tzeng EE, Geller DA, Billiar TR, Harris CC: p53 and vascular endothelial growth factor regulate tumor growth of NOS2-expressing human carcinoma cells. Nat Med 1998, 12:1371-1376.
• [13]Grisham MB, Jourd’heuil D, Wink DA: Nitric oxide: I.Physiological chemistry of nitric oxide and its metabolites: implications in inflammation. Gastrointest Liver Physiolo1 1999, 39:315-321.
• [14]Kanner J, Harel S, Granit R: Nitric oxide as an antioxidant. Arch Biochem Biophys 1991, 289(1):130-136.
• [15]Subapriya R, Kumaraguruparan R, Ramachandran CR, Nagini S: Oxidant-antioxidant status in patients with oral squamous cell carcinomas at different intraoral sites. Clin Biochem 2002, 35:489-493.
• [16]Tamir S, Tannenbaum SR: The role of nitric oxide (NO) in the carcinogenic process. Biochim Biophys Acta 1996, 1288:F31-F36.
• [17]Wink DA, Mitchell JB: The chemical biology of NO. Insights into regulation, protective and toxic mechanisms of nitric oxide. Free Radic Biol Med 1998, 25(4/5):434-456.
• [18]Patel RP, McAndrew J, Sellak H, White RC, Jo H, Freeman BA, Darley-Usmar VM: Biological aspects of reactive nitrogen species. Biochim Biophys Acta 1999, 1411:385-400.
• [19]de Rojas-Walker T, Tamir S, Ji H, Wishnok JS, Tannenbaum SR: Nitric oxide induces oxidative damage in addition to deamination in macrophage DNA. Chem Res Toxicol 1995, 8:473-477.
• [20]Gal A, Wogan GN: Mutagenesis associated with nitric oxide production in transgenic SJL mice. Proc Natl Acad Sci USA 1996, 93:15102-15107.
• [21]Wink DA, Vodovotz Y, Laval J, Laval F, Dewhirst MW, Mitchell JB: The multifaceted roles of nitric oxide in cancer. Carcinogenesis 1998, 19(5):711-721.
• [22]Sun Y: Free radicals, antioxidant enzymes and carcinogenesis. Free Radic Biol Med 1990, 8:583-599.
• [23]Wink DA, Kasprzak KS, Maragos CM, Elespuru RK, Misra M, Dunams TM, Cebula TA, Koch WH, Andrews AW, Allen JS: DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 1992, 254:1001-1003.
• [24]Choi BM, Pae HO, Jang SI, Kim YM, Chung HT: Nitric oxide as a pro-apoptotic as well as anti-apoptotic modulator. J Biochem Mol Biol 2002, 35:116-126.
• [25]Von KA, Brune B: Cyclooxygenase-2: an essential regulator of NO-mediated apoptosis. FASEBJ 1997, 11:887-895.
• [26]Ziche M, Morbidelli L: Nitric oxide and angiogenesis. J Neurooncol 2000, 50:139-148.
• [27]Lala PK, Orucevic A: Role of nitric oxide in tumor progression: lessons from experimental tumors. Cancer Metastasis Rev 1998, 17:91-106.
• [28]Breast Cancer Awareness Month in October (World Health Organization 2012). http://www.who.int/cancer/events/breast_cancer_month/en/ webcite
• [29]Loibl S, von Minckwitz G, Weber S, Sinn HP, Schini-Kerth VB, Lobysheva I, Nepveu F, Wolf G, Strebhardt K, Kaufmann M: Expression of endothelial and inducible nitric oxide synthase in benign and malignant lesions of the breast and measurement of nitric oxide using electron paramagnetic resonance spectroscopy. Cancer 2002, 95(6):1191-1198.
• [30]Alagol H, Erdem E, Sancak B, Turkmen G, Camlibel M, Bugdayci G: Nitric oxide biosynthesis and malondialdehyde levels in advanced breast cancer. Aust N Z J Surg 1999, 69(9):647-650.
• [31]Thomsen LL, Miles DW, Happerfield L, Bobrow LG, Knowles RG, Moncada S: Nitric oxide synthase activity in human breast cancer. Br J Cancer 1995, 72(1):41-44.
• [32]Jadeski LC, Hum KO, Chakraborty C, Lala PK: Nitric oxide promotes murine mammary tumour growth and metastasis by stimulating tumour cell migration, invasiveness and angiogenesis. Int J Cancer 2000, 86:30-39.
• [33]Nakamura Y, Yasuoka H, Tsujimoto M, Yoshidome K, Nakashara M, Nakao K, Nakamura M, Kakudo K: NO in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis. Clin Cancer Res 2006, 12(4):1201-1207.
• [34]Switzer CH, Cheng RY-S, Ridnour LA, Glynn SA, Ambs S, Wink DA: Ets-1 is a transcriptional mediator of oncogenic nitric oxide signalling in estrogen receptor negative breast cancer. Breast Cancer Res 2012, 14:R125.
• [35]Tschugguel W, Knogler W, Czerwenka K, Mildner M, Weninger W, Zeillinger R, Huber JC: Presence of endothelial calcium-dependent nitric oxide synthase in breast apocrine metaplasia. Br J Cancer 1996, 74:1423-1426.
• [36]Zeillinger R, Tantscher E, Schneeberger C, Tschugguel W, Eder S, Sliutz G, Huber JC: Simultaneous expression of nitric oxide synthase and estrogen receptor in human breast cancer cell lines. Breast Cancer Res Treat 1996, 40(2):205-207.
• [37]Pance A: Nitric oxide hormones and breast cancer. Nitric oxide and hormones in breast cancer: allies or enemies? Future Oncol 2006, 2(2):275-288.
• [38]Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics. CA Cancer J Clin 2005, 55:74-108.
• [39]zur Hausen H: Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2002, 2:342-350.
• [40]Benencia F, Gamba G, Cavalieri H, Courreges MC, Benedetti R, Villamil SM, Massouh EJ: Nitric oxide and HSV vaginal infection in BALB/c mice. Virology 2003, 309:75-84.
• [41]Carratelli CR, Rizzo A, Paolillo R, Catania MR, Catalanotti P, Rossano F: Effect of nitric oxide on the growth of Chlamydophilapneumoniae. Can J Microbiol 2005, 51(11):941-947.
• [42]Chang K, Lubo Z: Review article: steroid hormones and uterine vascular adaptation to pregnancy. Reprod Sci 2008, 15:336-348.
• [43]Naidu MSK, Suryakar AN, Swami SC, Katkam RV, Kumbar KM: Oxidative stress and antioxidant status in cervical cancer patients. Indian J Clin Biochem 2007, 22(2):140-144.
• [44]Beevi SS, Rasheed MH, Geetha A: Evidence of oxidative and nitrosative stress in patients with cervical squamous cell carcinoma. Clinica Chimica Acta 2007, 375(1–2):119-123.
• [45]Hiraku Y, Tabata T, Ma N, Murata M, Ding X, Kawanishi S: Nitrative and oxidative DNA damage in cervical intraepithelial neoplasia associated with human papilloma virus infection. Cancer Sci 2007, 98:964-972.
• [46]Tavares-Murta BM, de Resende AD, Cunha FQ, Murta EFC: Local profile of cytokines and nitric oxide in patients with bacterial vaginosis and cervical intraepithelial neoplasia. Eur J Obstet Gynecol Repro Biol 2008, 138:93-99.
• [47]Walboomers JMM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999, 189:12-19.
• [48]Wei L, Gravitt PE, Song H, Maldonado AM, Ozbun MA: Nitric oxide induces early viral transcription coincident with increased DNA damage and mutation rates in human papillomavirus-infected cells. Cancer Res 2009, 69:4878-4884.
• [49]Wei XM, Wang Q, Gao SJ, Sui L: Relationship between nitric oxide in cervical microenvironment and different HPV types and effect on cervical cancer cells. Zhonghua Fu Chan Ke Za Zhi 2011, 46(4):260-265.
• [50]Mulshine JL, Frank C, Melvyn S, De Luca LM: Lung cancer evolution to preinvasive management. Clin Chest Med 2002, 23(1):1-25.
• [51]Bilello KS, Murin S, Matthay RA: Epidemiology, etiology, and prevention of lung cancer. Clin Chest Med 2002, 23(1):1-25.
• [52]Masri FA, Comhair SAA, Koeck T, Xu W, Janocha A, Ghosh S, Dweik RA, Golish J, Kinter M, Stuehr DJ, Erzurum SC, Aulak KS: Abnormalities in nitric oxide and its derivatives in lung cancer. Am J Respir Crit Care Med 2005, 172:597-605.
• [53]Chen GG, Lee TW, Xu H, Yip JH, Li M, Mok TS, Yim AP: Increased inducible nitric oxide synthase in lung carcinoma of smokers. Cancer 2008, 112(2):372-381.
• [54]Puhakka AR, Harju TH, Paakko PK, Soini YM, Kinnula VL: Nitric oxide synthases are associated with bronchial dysplasia. Lung Cancer 2006, 51(3):275-282.
• [55]Forbes TA, Hopkins L, Schneider B, Lazarus L, Leitenberg D, Constant S, Schwartz A, Patierno S, Ceryak S: Potential role of nitric oxide in chromium-induced lung carcinogenesis. Cancer Res 2012, 72(8 Suppl):5456. Abstract
• [56]Beckman JS, Ischiropoulos H, Zhu L, van der Woerd M, Smith C, Chen J, Harrison J, Martin JC, Tsai M: Kinetics of superoxide dismutaseand iron-catalyzed nitration of phenolics by peroxynitrite. Arch Biochem Biophys 1992, 298:438-445.
• [57]Haddad IY, Pataki G, Hu P, Galliani C, Beckman JS, Matalon S: Quantitation of nitrotyrosine levels in lung sections of patients and animals with acute lung injury. J Clin Invest 1994, 94:2407-2413.
• [58]MacMillan-Crow LA, Crow JP, Kerby JD, Beckman JS, Thompson JA: Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. Proc Natl Acad Sci USA 1996, 93:11853-11858.
• [59]Cobbs CS, Whisenhunt TR, Wesemann DR, Harkins LE, Erwin G, Van M, Minu S: Inactivation of wild-type p53 protein function by reactive oxygen and nitrogen species in malignant gliomacells. Cancer Res 2003, 63:8670-8673.
• [60]Masri F: Role of nitric oxide and its metabolites as potential markers in lung cancer. Ann Thorac Med 2010, 5(3):123-127.
• [61]Correa P, Piazuelo MB, Camargo MC: The future of gastric cancer prevention. Gastric Cancer 2004, 7(1):9-16.
• [62]Calatayud S, Barrachina D, Esplugues JV: Nitric oxide: relation to integrity, injury, and healing of the gastric mucosa. Microsc Res Tech 2001, 53(5):325-335.
• [63]Yagihashi N, Kasajima H, Sugai S, Matsumoto K, Ebina Y, Morita T, Murakami T, Yagihashi S: Increased in situ expression of nitric oxide synthase in human colorectal cancer. Virchows Arch 2001, 436(2):109-114.
• [64]Feng CW, Wang LD, Jiao LH, Liu B, Zheng S, Xie XJ: Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features. BMC Cancer 2002, 2:8. 1–7
• [65]Correa P: Human gastric carcinogenesis. A multistep and multifactorial process–first American Cancer Society award lecture on cancer epidemiology and prevention. Cancer Res 1992, 52:6735-6740.
• [66]You WC, Blot WJ, Li JY, Chang YS, Jin ML, Kneller R, Zhang L, Han ZX, Zeng XR, Liu WD, Zhao L, Correa P, Fraumeni JF, Xu GW: Precancerous gastric lesions in a population at high risk of stomach cancer. Cancer Res 1993, 53:1317-1321.
• [67]Nardone G: Review article: Molecular basis of gastric carcinogenesis. Aliment Pharmacol Ther 2003, 17(Suppl. 2):75-81.
• [68]Parsonnet J, Friedman GD, Oremtreich N, Vogelman H: Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut 1997, 40:297-301.
• [69]Nomura A, Stemmermann GN, Chyou PH, Kato J, Perez-Perez GI, Blaser MJ: Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 1991, 325:1132-1136.
• [70]Watanabe T, Tada M, Nagai H, Sasaki S, Nakao M: Helicobacter pylori infection induces gastric cancer in Mongolian gerbils. Gastroenterol 1998, 115(3):642-648.
• [71]Honda S, Fujioka T, Tokieda M, Satoh R, Nishizono A, Nasu M: Development of Helicobacter pylori-induced gastric carcinoma in Mongolian gerbils. Cancer Res 1998, 58:4255-4259.
• [72]Nam KT, Oh SY, Ahn B, Kim YB, Jang DD, Yang KH, Hahm KB, Kim DY: Decreased Helicobacter pylori associated gastric carcinogenesis in mice lacking inducible nitric oxide synthase. Gut 2004, 53(9):1250-1255.
• [73]Fenoglio-Preiser CM, Wang J, Stemmermann GN, Noffsinger A: TP53 and gastric carcinoma: areview. Human Mutat 2003, 21:258-270.
• [74]Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannebaum SR: DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci USA 1992, 89:3030-3034.
• [75]Broholm H, Rubin I, Kruse A, Braendstrup O, Schmidt K, Skriver EB, Lauritzen M: Nitric oxide synthase expression and enzymatic activity in human brain tumors. Clin Neuropathol 2003, 22(6):273-281.
• [76]Cobbs CS, Brenman JE, Aldape KD, Bredt DS, Israel MA: Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res 1995, 55:727-730.
• [77]Nagpal JK, Das BR: Oral cancer: reviewing the present understanding of its molecular mechanism and exploring the future directions for its effective management. Oral Oncol 2003, 39:213-221.
• [78]Patel BP, Rawal UM, Rawal RM, Shukla SN, Patel PS: Tobacco, antioxidant enzymes, oxidative stress, and genetic susceptibility in oral cancer. Am J Clin Oncol 2008, 31(5):454-459.
• [79]Nair U, Bartsch H, Nair J: Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms. Mutagenesis 2004, 19(4):251-262.
• [80]Rasheed MH, Beevi SS, Geetha A: Enhanced lipid peroxidation and nitric oxide products with deranged antioxidant status in patients with head and neck squamous cell carcinoma. Oral Oncol 2007, 43:333-338.
• [81]Patel JB, Shah FD, Shukla SN, Shah PM, Patel PS: Role of nitric oxide and antioxidant enzymes in the pathogenesis of oral cancer. JCRT 2009, 5:247-253.
• [82]Korde SD, Basak A, Chaudhary M, Goyal M, Vagga A: Enhanced nitrosative and oxidative stress with decreased total antioxidant capacity in patients with oral precancer and oral squamous cell carcinoma. Oncology 2011, 80(5–6):382-389.
• [83]Hashibe M, Brennan P, Benhamou S, Castellsague X, Chen C, Curado MP, Dal Maso L, Daudt AW, Fabianova E, Fernandez L, Wünsch-Filho V, Franceschi S, Hayes RB, Herrero R, Koifman S, La Vecchia C, Lazarus P, Levi F, Mates D, Matos E, Menezes A, Muscat J, Eluf-Neto J, Olshan AF, Rudnai P, Schwartz SM, Smith E, Sturgis EM, Szeszenia-Dabrowska N, Talamini R: Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. J Natl Cancer Inst 2007, 99(10):777-789.
• [84]Cooper RG, Magwere T: Nitric oxide-mediated pathogenesis during nicotine and alcohol consumption. Indian J Physiol Pharmacol 2008, 52(1):11-18.
• [85]Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D: Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 2000, 92(9):709-720.
• [86]Pintos J, Black MJ, Sadeghi N, Ghadirian P, Zeitouni AG, Viscidi RP, Herrero R, Coutlée F, Franco EL: Human papillomavirus infection and oral cancer: a case–control study in Montreal. Canada. Oral Oncol 2008, 44(3):242-250.
• [87]D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML: Case–control study of human papillomavirus and oropharyngeal cancer. New Engl J Med 2007, 356(19):1944-1956.
• [88]Joura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Garland SM, Harper DM, Tang GW, Ferris DG, Steben M, Jones RW, Bryan J, Taddeo FJ, Bautista OM, Esser MT, Sings HL, Nelson M, Boslego JW, Sattler C, Barr E, Paavonen J: Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against highgradevulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet 2007, 369(9574):1693-1702.
• [89]Adelstein DJ, Ridge JA, Gillison ML, Chaturvedi AK, D'Souza G, Gravitt PE, Westra W, Psyrri A, Kast WM, Koutsky LA, Giuliano A, Krosnick S, Trotti A, Schuller DE, Forastiere A, Ullmann CD: Head and neck squamous cell cancer and the human papillomavirus: summary of a National Cancer Institute State of the Science Meeting, November 9–10, 2008, Washington, D.C. Head Neck 2009, 31(11):1393-1422.
• [90]Li LM, Kibourn RG, Adams J, Filder IJ: Role of NO in lysis of tumor cells by cytokine activated endothelial cells. Cancer Res 1991, 51:2531-2535.
• [91]Shang ZJ, Li JR: Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in oral squamous cell carcinoma: its correlation with angiogenesis and disease progression. J Oral Pathol Med 2005, 4:134-139.
• [92]Lechner M, Lirk P, Rieder J: Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin. Semin Cancer Biol 2005, 15:277-289.
• [93]Lepoivre M, Flaman JM, Henry Y: Early loss of the tyrosyl radical in ribonucleotidereductase of adenocarcinoma cells producing nitric oxide. J Biol Chem 1992, 267:22994-23000.
• [94]Aranda E, López-Pedrera C, De La Haba-Rodríguez JR, Rodríguez-Ariza A: Nitric oxide and cancer: the emerging role of S nitrosylation. Curr Mol Med 2012, 12:50-67.
• [95]Baritaki S, Huerta-Yepez S, Sahakyan A, Karagiannides I, Bakirtzi K, Jazirehi A, Bonavida B: Mechanisms of nitric oxide-mediated inhibition of EMT in cancer: inhibition of the metastasis-inducer Snail and induction of the metastasis-suppressor RKIP. Cell Cycle 2010, 9:4931-4940.
• [96]Bonavida B: Inhibition of epithelial-to-mesenchymal transition (EMT) in cancer by nitric oxide: pivotal roles of nitrosylation of NF-κB, YY1 and Snail. For Immunopathol Dis Therap 2012, 3(2):125-133.
• [97]Zhao SF, Tong XY, Zhu FD: Nitric oxide induces oral squamous cell carcinoma cells apoptosis with p53 accumulation. Oral Oncol 2005, 41(8):785-790.
• [98]Brennan PA, Palacios-Callender M, Umar T, Tant S, Langdon JD: Expression of type 2 nitric oxide synthase and p21 in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 2002, 31(2):200-205.
• [99]Gallo O, Emanuela M, Lucia M, Franchi A, Fini-storchi I, Vergari WA, Ziche M: Role of NO in angiogenesis and tumor progression in head and neck cancer. J Natl Cancer Inst 1998, 90:587-596.
• [100]Korde(Choudhari) S, Sridharan G, Gadbail A, Poornima V: Nitric oxide and oral cancer: A review. Oral Oncol 2012, 48:475-483.
• [101]Singh S, Gupta AK: Mini review nitric oxide: role in tumour biology and iNOS/NO-based anticancer therapies. Cancer Chemother Pharmacol 2011, 67(6):1211-1224.
• [102]Lehrman S: Virus treatment questioned after gene therapy death. Nature 1991, 401:517-518.
• [103]Huerta S, Chilka S, Bonavida B: Nitric oxide donors: novel cancer therapeutics (Review). Int J Oncol 2008, 33:909-927.
• [104]Bonavida B, Baritaki S, Huerta-Yepez S, Vega MI, Chatterjee D, Yeung K: Novel therapeutic applications of nitric oxide donors in cancer: roles in chemo- and immunosensitization to apoptosis and inhibition of metastases. Nitric oxide 2008, 19(2):152-157.
• [105]Yasuda H, Yamaya M, Nakayama K, Sasaki T, Ebihara S, Kanda A, Asada M, Inoue D, Suzuki T, Okazaki T, Takahashi H, Yoshida M, Kaneta T, Ishizawa K, Yamanda S, Tomita N, Yamasaki M, Kikuchi A, Kubo H, Sasaki H: Randomized phase II trial comparing nitroglycerin plus vinorelbine and cisplatin with vinorelbine and cisplatin alone in previously untreated stage IIIB/IV non-small-cell lung cancer. J Clin Oncol 2006, 24:688-694.
• [106]Yasuda H, Nakayama K, Watanabe M, Suzuki S, Fuji H, Okinaga S, Kanda A, Zayasu K, Sasaki T, Asada M, Suzuki T, Yoshida M, Yamanda S, Inoue D, Kaneta T, Kondo T, Takai Y, Sasaki H, Yanagihara K, Yamaya M: Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma. Clin Cancer Res 2006, 12:6748-6757.
• [107]Bonavida B, Baritaki S: Dual role of NO donors in the reversal of tumor cell resistance and EMT: downregulation of the NF-jB/Snail/YY1/RKIP circuitry. Nitric Oxide 2011, 24(1):1-7.
• [108]Lee DH, Pfeifer GP: Mutagenesis induced by the nitric oxide donor sodium nitroprusside in mouse cells. Mutagenesis 2007, 22:63-67.
• [109]Rigas B: Novel agents for cancer prevention based on nitric oxide. Biochem Soc Trans 2007, 35:136-138.
• [110]Frost MC, Reynolds MM, Meyerhoff ME: Polymers incorporating nitric oxide releasing/generating substances for improved biocompatibility of blood-contacting medical devices. Biomaterials 2005, 26(14):1685-1693.
• [111]Seabra AB, Duran N: Nitric oxide-releasing vehicles for biomedical applications. J Mater Chem 2010, 20(9):1624-1637.
• [112]Saraiva J, Marotta-Oliveira SS, Cicillini SA, de Oliveira Eloy J, Marchett JM: Nanocarriers for nitric oxide delivery. J Drug Deliv 2011, 1:1-16.
• [113]Quintanar-Guerrero D, Ganem-Quintanar A, Allemann E, Fessi H, Doelker E: Influence of the stabilizer coating layer on the purification and freeze-drying of poly(D, Llactic acid) nanoparticles prepared by an emulsion-diffusion technique. J Microencapsul 1998, 15(1):107-119.
• [114]Jain R, Shah NH, Malick AW, Rhodes CT: Controlled drug delivery by biodegradable poly(ester) devices: different preparative approaches. Drug DevInd Pharm 1998, 24(8):703-727.
• [115]Kanayama N, Yamaguchi K, Nagasaki Y: PEGylated polymer micelle-based nitric oxide (NO) photodonor with NO-mediated antitumor activity. Chem Lett 2010, 39(9):1008-1009.
• [116]Friedman AJ, Han G, Navati MS, Chacko M, Gunther L, Alfieri A, Friedman JM: Sustained release nitric oxide releasing nanoparticles: characterization of a novel delivery platform based on nitrite containing hydrogel/glass composites. Nitric Oxide 2008, 19(1):12-20.
• [117]Cabrales P, Han G, Roch eC, Nacharaju P, Friedman AJ, Friedman JM: Sustained release nitric oxide from long-lived circulating nanoparticles. Free Radical Bio Med 2010, 49(4):530-538.
• [118]Marquele-Oliveira F, Santana DC, Taveira SF, Vermeulen DM, de Oliveira AR, da Silva RS, Lopez RF: Development of nitrosyl ruthenium complex-loaded lipid carriers for topical administration: improvement in skin stability and in nitric oxide release by visible light irradiation. J Pharm Biomed Anal 2010, 53(4):843-851.
• [119]Stevens EV, Carpenter AW, Shin JH, Liu J, Der CJ, Schoenfisch MH: Nitric oxide-releasing silica nanoparticle inhibition of ovarian cancer cell growth. Mol Pharmaceutics 2010, 7(3):775-785.
• [120]Yatvin MB, Weinstein JN, Dennis WH, Blumenthal R: Design of liposomes for enhanced local release of drugs by hyperthermia. Science 1978, 202(4374):1290-1293.
• [121]Wang J, Teng Y, Hao Y, Oh-Lee J, Mohanty DK: Preparation and properties of polyamines: part IIcontrolled and sustained release of nitric oxide (NO) from nitrosated polymers. Polym J 2009, 41(9):715-725.
• [122]Medintz IL, Uyeda HT, Goldman ER, Mattoussi H: Quantum dot bioconjugates for imaging, labelling and sensing. Nat Mater 2005, 4(6):435-446.
• [123]Cicillini SA, Prazias ACL, Tedesco AC, Serra OA, da Silva RS: Nitric oxide and singlet oxygen photo-generation by light irradiation in the phototherapeutic window of a nitrosyl ruthenium conjugated with a phthalocyanine rare earth complex. Polyhedron 2009, 28(13):2766-2770.
• [124]Neuman D, Ostrowski AD, Absalonson RO, Strouse GF, Ford PC: Photosensitized NO release from water soluble nanoparticle assemblies. J Am Chem Soc 2007, 129(14):4146-4147.
• [125]Hien T, Duong T, Kamarudin ZM, Erlich RB, Li Y, Jones MW, Kavallaris M, Boyer C, Davis TP: Intracellular nitric oxide delivery from stable NO-polymeric nanoparticle carriers. Chem Commun 2013, 49:4190-4192.
• [126]Giles NM, Kumari S, Gang BP, Yuen CW, Billaud EM, Giles GI: The molecular design of S-nitrosothiols as photodynamic agents for controlled nitric oxide release. Chem Biol Drug Des 2012, 80(3):471-478.