Abstract
Nitric oxide (NO) is an inorganic, colorless gas, with good stability in water. NO is generated by a family of enzymes, termed NO synthases (NOS) and the distribution of the different NOS isoforms is largely related to their respective functions. Vascular endothelial NOS (eNOS) is important for cardiovascular homeostasis, vessel remodeling and angiogenesis; neuronal NOS (nNOS) is expressed in neurons, primarly in the cerebellum and hippocampus and implicated in glutamatergic neurotransmission. Inducible NOS (iNOS) is believed to be of fundamental importance to inflammatory processes. An increased activity of iNOS isoform has been found in several tumors; however, the role of NO in cell proliferation and apoptosis is still not fully elucidated. In fact, the actions of NO on cancer are dichotomous in that effects consistent with cancer promotion and prevention or reversion have been reported. Moreover, iNOS and COX-2 have been found to be co-expressed within the same tumor cells and involved in the regulation of tumor growth. In conclusion, iNOS and COX-2 products may represent a common final pathway controlling different tumorigenic mechanism.
Keywords
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Aisaka, K., Gross, S.S., Griffith, O.W., and Levi, R. (1989). l-arginine availability determines the duration of acetylcholine-induced systemic vasodilation In Vivo. Biochem. Biophys. Res. Commun. 163, 710–717.
Altieri, D.C. (2008a). New wirings in the survivin networks. Oncogene 27, 6276–6284.
Altieri, D.C. (2008b). Survivin, cancer networks and pathway-directed drug discovery. Nat. Rev. Cancer. 8, 61–70.
Ambrose, M., Ryan, A., O'Sullivan, G.C., Dunne, C., and Barry, O.P. (2006). Induction of apoptosis in renal cell carcinoma by reactive oxygen species: involvement of extracellular signal-regulated kinase 1/2, p38delta/gamma, cyclooxygenase-2 down-regulation, and translocation of apoptosis-inducing factor. Mol. Pharmacol. 69, 1879–1890.
Bak, A.W., McKnight, W., Li, P., Del Soldato, P., Calignano, A., Cirino, G., and Wallace, J.L. (1998). Cyclooxygenase-independent chemoprevention with an aspirin derivative in a rat model of colonic adenocarcinoma. Life Sci. 62, 367–373.
Baylis, C., Mitruka, B., and Deng, A. (1992). Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage. J. Clin. Invest. 90, 278–281.
Beckman, J.S., Beckman, T.W., Chen, J., Marshall, P.A., and Freeman, B.A. (1990). Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc. Natl. Acad. Sci. USA. 87, 1620–1624.
Beckman, J.S. and Koppenol, W.H. (1996). Nitric Oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am. J. Physiol. 271, 1424–1437.
Bogle, R.G., Moncada S., Pearson, J.D., and Mann, G.E. (1992). Identification of inhibitors of nitric oxide synthase that do not interact with the endothelial cell l-arginine transporter. Br. J. Pharmacol. 105, 768–770.
Bredt, D.S. and Snyder, S.H. (1990). Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc. Natl. Acad. Sci. USA. 87, 682–685.
Butler, A.R. and Williams, D.L.H. (1993). The physiological role of nitric oxide. Chem. Soc. Reviews 1, 233–241.
Calver, A., Collier, J., and Vallance, P. (1993). Nitric oxide and cardiovascular control. Exp. Physiol. 78, 303–326.
Chartrain, N.A., Geller, D.A., Koty, P.P., Sitrin, N.F., Nussler, A.K. et al. (1994). Molecular cloning, structure, and chromosomal localization of the human inducible nitric oxide synthase gene. J. Biol. Chem. 269, 6765–6772.
Chiou, G.C. (2001). Review: effects of nitric oxide on eye diseases and their treatment. J. Ocul. Pharmacol. Ther. 17, 189–198.
Cho, A.K., Lindeke, B., Hodshon, B.J. (1972). The N-hydroxylation of phentermine (2-methyl-1-phenylisopropylamine) by rabbit liver microsomes. Res. Commun. Chem. Pathol. Pharmacol. 4, 519–528.
Cianchi, F., Perna, F., and Masini, E. (2005). iNOS/COX-2 Pathway Interaction: a Good Molecular Target for Cancer Treatment. Curr. Enzyme Inhib. 1, 97–105.
Cianchi, F., Cortesini, C., Fantappiè, O., Messerini, L., Sardi, I., Lasagna, N., Perna, F., Fabbroni, V., Di Felice, A., Perigli, G., Mazzanti, R., Masini, E. (2004). Cyclooxygenase-2 activation mediates the proangiogenic effect of nitric oxide in colorectal cancer. Clin. Cancer Res. 10, 2694–2704.
Cobbs, C.S., Brenman, J.E., Aldape, K.D., Bredt, D.S., and Israel, M.A. (1995). Expression of nitric oxide synthase in human central nervous system tumors. Cancer. Res. 55, 727–730.
Connor, J.R., Manning, P.T., Settle, S.L., Moore, W.M., Jerome, G.M., Webber, R.K., Tjoeng, F.S., and Currie, M.G. (1995). Suppression of adjuvant-induced arthritis by selective inhibition of inducible nitric oxide synthase. Eur. J. Pharmacol. 273, 15–24.
Corbett, J.A., Kwon, G., Turk, J., and McDaniel, M.L. (1993). IL-1 beta induces the coexpression of both nitric oxide synthase and cyclooxygenase by islets of langerhans: activation of cyclooxygenase by nitric oxide. Biochemistry 32, 13767–13770.
Cuzzocrea, S., Zingarelli, B., Hake, P., Salzman, A.L., and Szabo, C. (1998). Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation. Free Radic. Biol. Med. 24, 450–459.
Cuzzocrea, S., Misko, T.P., Costantino, G., Mazzon, E., Micali, A., Caputi, A.P., Macarthur, H., and Salvemini, D. (2000). Beneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion. FASEB J. 14, 1061–1072.
Cuzzocrea, S., McDonald, M.C., Mazzon, E., Filipe, H.M., Centorrino, T., Lepore, V., Terranova, M.L., Ciccolo, A., Caputi, A.P., and Thiemermann, C. (2001). Beneficial effects of tempol, a membrane-permeable radical scavenger, on the multiple organ failure induced by zymosan in the rat. Crit. Care Med. 29, 102–111.
De Caterina, R., Libby, P., Peng, H.B., Thannickal, V.J., Rajavashisth, T.B., Gimbrone, M.A., Jr., Shin, W.S., and Liao, J.K. (1995). Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J. Clin. Invest. 96, 60–68.
Di Rosa, M., Radomski, M., Carnuccio, R., and Moncada S. (1990). Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages. Biochem. Biophys. Res. Commun. 172, 1246–1252.
Dong, Z., Staroselsky, A.H., Qi, X., Xie, K., and Fidler, I.J. (1994). Inverse correlation between expression of inducible nitric oxide synthase activity and production of metastasis in K-1735 murine melanoma cells. Cancer Res. 54, 789–793.
Donnini, S., Morbidelli, L., Taraboletti, G., and Ziche, M. (2004). ERK1-2 and p38 MAPK regulate MMP/TIMP balance and function in response to thrombospondin-1 fragments in the microvascular endothelium. Life Sci. 74, 2975–2985.
Egan, R.W., Paxton, J., and Kuehl, F.A., Jr. (1976). Mechanism for irreversible self-deactivation of prostaglandin synthetase. J. Biol. Chem. 251, 7329–7335.
Feldman, P.L., Griffith, O.W., Hong, H., and Stuehr, D.J. (1993). Irreversible inactivation of macrophage and brain nitric oxide synthase by L-NG-methylarginine requires NADPH-dependent hydroxylation. J. Med. Chem. 36, 491–496.
Feron, O., Belhassen, L., Kobzik, L., Smith, T.W., Kelly, R.A., and Michel, T. (1996). Endothelial nitric oxide synthase targeting to caveolae. specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J. Biol. Chem. 271, 22810–22814.
Fetz, V., Bier, C., Habtemichael, N., Schuon, R., Schweitzer, A., Kunkel, M., Engels, K., Kovács, A.F., Schneider, S., Mann, W., Stauber, R.H., and Knauer, S.K. (2009). Inducible NO synthase confers chemoresistance in head and neck cancer by modulating survivin. Int. J. Cancer 124, 2033–2041.
Franchi, A., Santucci, M., Masini, E., Sardi, I., Paglierani, M., and Gallo, O. (2002). Expression of matrix metalloproteinase 1, matrix metalloproteinase 2, and matrix metalloproteinase 9 in carcinoma of the head and neck. Cancer 95, 1902–1910.
Fu, S., Ramanujam, K.S., Wong, A., Fantry, G.T., Drachenberg, C.B., James, S.P., Meltzer, S.J., and Wilson, K.T. (1999). Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology 116, 1319–1329.
Fukumura, D., Kashiwagi, S., and Jain, R.K. (2006). The role of nitric oxide in tumour progression. Nat. Rev. Cancer 6, 521–534.
Fukuto, J.M., Stuehr, D.J., Feldman, P.L., Bova, M.P., and Wong, P. (1993). Peracid oxidation of an N-hydroxyguanidine compound: a chemical model for the oxidation of N omega-hydroxyl-L-arginine by nitric oxide synthase. J. Med. Chem. 36, 2666–2670.
Fulton, D., Gratton, J.P. and Sessa, W.C. (2001). Post-translational control of endothelial nitric oxide synthase: why isn’t calcium/calmodulin enough? J. Pharmacol. Exp. Ther. 299, 818–824.
Gallo, O., Masini, E., Morbidelli, L., Franchi, A., Fini-Storchi, I., Vergari, W.A., and Ziche, M. (1998). Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer. J. Natl. Cancer Inst. 90, 587–596.
Gallo, O., Schiavone, N., Papucci, L., Sardi, I., Magnelli, L., Franchi, A., Masini, E., and Capaccioli, S. (2003). Down-regulation of nitric oxide synthase-2 and cyclooxygenase-2 pathways by p53 in squamous cell carcinoma. Am. J. Pathol. 163, 723–732.
Garg, U.C. and Hassid, A. (1989). Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J. Clin. Invest. 83, 1774–1777.
Garthwaite, G., and Garthwaite, J. (1991). Mechanisms of AMPA neurotoxicity in rat brain slices. Eur. J. Neurosci. 3, 729–736.
Garthwaite, J. and Boulton, C.L. (1995). Nitric oxide signaling in the central nervous system. Annu. Rev. Physiol. 57, 683–706.
Gibson, N.J., Rössler, W., Nighorn, A.J., Oland, L.A., Hildebrand, J.G., and Tolbert, L.P. (2001). Neuron-glia communication via nitric oxide is essential in establishing antennal-lobe structure in Manduca sexta. Dev. Biol. 240, 326–339.
Gilligan, D.M., Panza, J.A., Kilcoyne, C.M., Waclawiw, M.A., Casino, P.R., and Quyyumi, A.A. (1994). Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation. Circulation. 90, 2853–2858.
Grisham, M.B., Jourd'heuil, D., and Wink, D.A. (1999). Nitric oxide. I. physiological chemistry of nitric oxide and its metabolites: implications in inflammation. Am. J. Physiol. 276, 315–321.
Hara, A. and Okayasu, I. (2004). Cyclooxygenase-2 and inducible nitric oxide synthase expression in human astrocytic gliomas: correlation with angiogenesis and prognostic significance. Acta Neuropathol. 108, 43–48.
Heneka, M.T., Loschmann, P.A., Gleichmann, M., Weller, M., Schulz, J.B., Wullner, U., and Klockgether, T. (1998). Induction of nitric oxide synthase and nitric oxide-mediated Apoptosis in neuronal PC12 cells after stimulation with tumor necrosis factor-alpha/lipopolysaccharide. J. Neurochem. 71, 88–94.
Hobbs, A.J., Higgs, A., and Moncada, S. (1999). Inhibition of nitric oxide synthase as a potential therapeutic target. Annu. Rev. Pharmacol. Toxicol. 39, 191–220.
Hood, J. and Granger, H.J. (1998). Protein kinase G mediates vascular endothelial growth factor-induced Raf-1 activation and proliferation in human endothelial cells. J. Biol. Chem. 273, 23504–23508.
Hori, K., Burd, P.R., Furuke, K., Kutza, J., Weih, K.A., and Clouse, K.A. (1999). Human immunodeficiency virus-1-infected macrophages induce inducible nitric oxide synthase and nitric oxide (NO) production in astrocytes: astrocytic NO as a possible mediator of neural damage in acquired immunodeficiency syndrome. Blood 93, 1843–1850.
Huang, P.L., Huang, Z., Mashimo, H., Bloch, K.D., Moskowitz, M.A., Bevan, J.A., and Fishman, M.C. (1995). Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature. 377, 239–242.
Huerta, S., Baay-Guzman, G., Gonzalez-Bonilla, C.R., Livingston, E.H., Huerta-Yepez, S., Bonavida, B. (2009) In vitro and in vivo sensitization of SW620 metastatic colon cancer cells to CDDP-induced apoptosis by the nitric oxide donor DETANONOate: involvement of AIF. Nitric Oxide 20, 182–194.
Iadecola, C., Zhang, F., Casey, R., Nagayama, M., and Ross, M.E. (1997). Delayed reduction of ischemic brain injury and neurological deficits in mice lacking the inducible nitric oxide synthase gene. J. Neurosci. 17, 9157–9164.
Ignarro, L.J., Buga, G.M., Wood, K.S., Byrns, R.E., and Chaudhuri, G. (1987). Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc. Natl. Acad. Sci. USA. 84, 9265–9269.
Ignarro, L.J., Fukuto, J.M., Griscavage, J.M., Rogers, N.E., and Byrns, R.E. (1993). Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from l-arginine. Proc. Natl. Acad. Sci. USA. 90, 8103–8107.
Inoue, T., Fukuo, K., Morimoto, S., Koh, E., and Ogihara, T. (1993). Nitric oxide mediates interleukin-1-induced prostaglandin E2 production by vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 194, 420–424.
Ishimura, N., Bronk, S.F., and Gores, G.J. (2004). Inducible nitric oxide synthase upregulates cyclooxygenase-2 in mouse cholangiocytes promoting cell growth. Am. J. Physiol. Gastrointest. Liver Physiol. 287, 88–95.
Ischiropoulos, H., Zhu, L., and Beckman, J.S. (1992). Peroxynitrite formation From macrophage-derived nitric oxide. Arch. Biochem. Biophys. 298, 446–451.
Jijon, H.B., Churchill, T., Malfair, D., Wessler, A., Jewell, L.D., Parsons, H.G., and Madsen, K.L. (2000). Inhibition of poly(ADP-ribose) polymerase attenuates inflammation in a model of chronic colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 279, 641–651.
Joshi, M., Strandhoy, J., and White, W.L. (1996). Nitric oxide synthase activity is up-regulated in melanoma cell lines: a potential mechanism for metastases formation. Melanoma Res. 6, 121–126.
Klimp, A.H., Hollema, H., Kempinga, C., Van der Zee, A.G., De Vries, E.G., and Daemen, T. (2001). Expression of cyclooxygenase-2 and inducible nitric oxide synthase in human ovarian tumors and tumor-associated macrophages. Cancer Res. 61, 7305–7309.
Knowles, R.G. and Moncada, S. (1994). Nitric oxide synthases in mammals. Biochem. J. 298, 249–258.
Kobzik, L., Bredt, D.S., Lowenstein, C.J., Drazen, J., Gaston, B., Sugarbaker, D., and Stamler, J.S. (1993). Nitric oxide synthase in human and rat lung: immunocytochemical and histochemical localization. Am. J. Respir. Cell. Mol. Biol. 9, 371–377.
Koki, A.T., Leahy, K.M., Harmon, J.M, and Masferrer, J.L. (2003). Cyclooxygenase-2 and cancer. In Harris, R.E. (ed.), COX-2 blockade in cancer prevention and therapy (pp. 185–203). Totowa: Humana Press.
Kong, G., Kim, E.K., Kim, W.S., Lee, K.T., Lee, Y.W., Lee, J.K., Paik, S.W., and Rhee, J.C. (2002). Role of cyclooxygenase-2 and inducible nitric oxide synthase in pancreatic cancer. J. Gastroenterol. Hepatol. 17, 914–921.
Kubes, P, Suzuki, M., and Granger, D.N. (1991). Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc. Natl. Acad. Sci. USA. 88, 4651–4655.
Kurose, I., Kubes, P., Wolf, R., Anderson, D.C., Paulson, J., Miyasaka, M., and Granger, D.N. (1993). Inhibition of nitric oxide production. mechanisms of vascular albumin leakage. Circ. Res. 73, 164–171.
Kwon, N.S., Nathan, C.F., Gilker, C., Griffith, O.W., Matthews, D.E., and Stuehr, D.J. (1990). L-citrulline production from l-arginine by macrophage nitric oxide synthase. The ureido oxygen derives from dioxygen. J. Biol. Chem. 265, 13442–13445.
Lancaster, J.R., Jr. and Hibbs, J.B., Jr. (1990). EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages. Proc. Natl. Acad. Sci. USA. 87, 1223–1227.
Landino, L.M., Crews, B.C., Timmons, M.D., Morrow, J.D., and Marnett, L.J. (1996). Peroxynitrite, the coupling product of nitric oxide and superoxide, activates prostaglandin biosynthesis. Proc. Natl. Acad. Sci. USA. 93, 15069–15074.
Lane, P. and Gross, S.S. (2002). Disabling a C-terminal autoinhibitory control element in endothelial nitric-oxide synthase by phosphorylation provides a molecular explanation for activation of vascular NO synthesis by diverse physiological stimuli. J. Biol. Chem. 277, 19087–19094.
Lee, P.C., Salyapongse, A.N., Bragdon, G.A., Shears, L.L., Watkins, S.C., Edington, H.D., and Billiar, T.R. (1999). Impaired wound healing and angiogenesis in ENOS-deficient mice. Am. J. Physiol. 277, 1600–1608.
Lee, J., Ryu, H., Ferrante, R.J., Morris, S.M., Jr., and Ratan, R.R. (2003). Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox. Proc. Natl. Acad. Sci. USA. 100, 4843–4848.
Lepoivre, M., Chenais B., Yapo, A., Lemaire, G., Thelander, L., and Tenu, J.P. (1990). Alterations of ribonucleotide reductase activity following induction of the nitrite-generating pathway in adenocarcinoma cells. J. Biol. Chem. 265, 14143–14149.
Li, H.L., Sun, B.Z., and Ma, F.C. (2004). Expression of COX-2, iNOS, p53 and Ki-67 in gastric mucosa-associated lymphoid tissue lymphoma. World J. Gastroenterol. 10, 1862–1866.
Liu, B. and Neufeld, A.H. (2000). Expression of nitric oxide synthase-2 (NOS-2) in reactive astrocytes of the human glaucomatous optic nerve head. Glia 30, 178–186.
Liu, Q., Chan, S.T., and Mahendran, R. (2003). Nitric oxide induces cyclooxygenase expression and inhibits cell growth in colon cancer cell lines. Carcinogenesis 24, 637–642.
Liu, Y., Borchert, G.L., and Phang, J.M. (2004). Polyoma enhancer activator 3, an ets transcription factor, mediates the induction of cyclooxygenase-2 by nitric oxide in colorectal cancer cells. J. Biol. Chem. 279: 18694–18700.
Loke, K.E., McConnell, P.I., Tuzman, J.M., Shesely, E.G., Smith, C.J., Stackpole, C.J., Thompson, C.I., Kaley, G., Wolin, M.S., and Hintze, T.H. (1999). Endogenous endothelial nitric oxide synthase-derived nitric oxide is a physiological regulator of myocardial oxygen consumption. Circ. Res. 84, 840–845.
Marrogi, A.J., Travis, W.D., Welsh, J.A., Khan, M.A., Rahim, H., Tazelaar, H., Pairolero, P., Trastek, V., Jett, J., Caporaso, N.E., Liotta, L.A., and Harris, C.C. (2000). Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of non-small cell lung carcinoma. Clin. Cancer Res. 6, 4739–4744.
Millan, A. and Huerta, S. (2009). Apoptosis-inducing factor and colon cancer. J. Surg. Res. 151, 163–170.
Miranda, K.M., Nims, R.W., Thomas, D.D., Espey, M.G., Citrin, D., Bartberger, M.D., Paolocci, N., Fukuto, J.M., Feelisch, M., and Wink, D.A. (2003). Comparison of the reactivity of nitric oxide and nitroxyl with heme proteins. A chemical discussion of the differential biological effects of these redox related products of NOS. J. Inorg. Biochem. 93, 52–60.
Mollace, V., Muscoli, C., Masini, E., Cuzzocrea, S., and Salvemini, D. (2005). Modulation of prostaglandin biosynthesis by nitric oxide and nitric oxide donors. Pharmacol. Rev. 57, 217–252.
Moore, W.M., Webber, R.K., Jerome, G.M., Tjoeng, F.S., Misko, T. P., and Currie, M.G. (1994). L-N6-(1-iminoethyl)lysine: a selective inhibitor of inducible nitric oxide synthase. J. Med. Chem. 37, 3886–3888.
Mulsch, A., Schray-Utz, B., Mordvintcev, P.I., Hauschildt, S., and Busse, R. (1993). Diethyldithiocarbamate inhibits induction of macrophage NO synthase. FEBS Lett. 321, 215–218.
Nadaud, S., Laumonnier, Y., and Soubrier F. (2000). Molecular aspects of the expression and regulation of endothelial nitric oxide synthase. J. Soc. Biol. 194, 131–135.
Nakane, M., Schmidt, H.H., Pollock, J.S., Forstermann, U., and Murad, F. (1993). Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett. 316, 175–180.
Nathan, C. (1992). Nitric Oxide As a Secretory Product of Mammalian Cells. FASEB J. 6, 3051–3064.
Nathan, C. and Xie, Q.W. (1994). Nitric oxide synthases: roles, tolls, and controls. Cell 78: 915–918.
Notoya. K., Jovanovic, D.V., Reboul, P., Martel-Pelletier, J., Mineau, F., and Pelletier, J.P. (2000). The induction of cell death in human osteoarthritis chondrocytes by nitric oxide is related to the production of prostaglandin E2 via the induction of cyclooxygenase-2. J. Immunol. 165, 3402–3410.
Palmer, R.M., Ferrige, A.G., and Moncada, S. (1987). Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327, 524–526.
Peng, H.B., Libby, P., and Liao, J.K. (1995). Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa B. J. Biol. Chem. 270, 14214–14219.
Pratt, M.A., Niu, M.Y., and Renart, L.I. (2006). Regulation of survivin by retinoic acid and its role in paclitaxel-mediated cytotoxicity in MCF-7 breast cancer cells. Apoptosis 11, 589–605.
Radi, R., Beckman, J.S., Bush, K.M., and Freeman, B.A. (1991). Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch. Biochem. Biophys. 288, 481–487.
Rajnakova, A., Moochhala, S., Goh, P.M., and Ngoi, S. (2001). Expression of nitric oxide synthase, cyclooxygenase, and p53 in different stages of human gastric cancer. Cancer Lett. 172: 177–185.
Rao, C.V., Indranie, C., Simi, B., Manning, P.T., Connor, J.R., and Reddy, B.S. (2002). Chemopreventive properties of a selective inducible nitric oxide synthase inhibitor in colon carcinogenesis, administered alone or in combination with celecoxib, a selective cyclooxygenase-2 inhibitor. Cancer Res. 62, 165–170.
Rao, C.V. (2004). Nitric oxide signaling in colon cancer chemoprevention. Mutat. Res. 555, 107–119.
Raspollini, M.R., Amunni, G., Villanucci, A., Boddi, V., Baroni, G., Taddei, A., and Taddei, G.L. (2004). Expression of inducible nitric oxide synthase and cyclooxygenase-2 in ovarian cancer: correlation with clinical outcome. Gynecol. Oncol. 92, 806–812.
Rees, D.D., Palmer, R.M., Hodson, H.F., and Moncada, S. (1989). A specific inhibitor of nitric oxide formation from l-arginine attenuates endothelium-dependent relaxation. Br. J. Pharmacol. 96, 418–424.
Rossi, F. and Bianchini, E. (1996). Synergistic induction of nitric oxide by beta-amyloid and cytokines in astrocytes. Biochem. Biophys. Res. Commun. 225, 474–478.
Salvemini, D., Settle, S.L., Masferrer, J.L., Seibert, K., Currie, M.G., and Needleman, P. (1995). Regulation of prostaglandin production by nitric oxide; an in vivo analysis. Br. J. Pharmacol. 114, 1171–1178.
Salvemini, D. and Masferrer, J.L. (1996). Interactions of nitric oxide with cyclooxygenase: in vitro, ex vivo, and in vivo studies. Methods Enzymol. 269, 12–25.
Salvucci, O., Carsana, M., Bersani, I., Tragni, G., and Anichini, A. (2001). Antiapoptotic role of endogenous nitric oxide in human melanoma cells. Cancer Res. 61, 318–326.
Sessa, W.C., Harrison, J.K., Barber, C.M., Zeng, D., Durieux, M.E., D'Angelo, D.D., Lync, K.R., and Peach, M.J. (1992). Molecular cloning and expression of a CDNA encoding endothelial cell nitric oxide synthase. J. Biol. Chem. 267, 15274–15276.
Sessa, W.C. (2004). eNOS at a glance. J. Cell. Sci. 117, 2427–2429.
Sherman, P.A., Laubach, V.E., Reep, B.R., and Wood, E.R. (1993). Purification and CDNA sequence of an inducible nitric oxide synthase from a human tumor cell line. Biochemistry 32, 11600–11605.
Simmons, M.L. and Murphy, S. (1994). Roles for protein kinases in the induction of nitric oxide synthase in astrocytes. Glia. 11, 227–234.
Sneddon, J.M. and Vane, J.R. (1988). Endothelium-derived relaxing factor reduces platelet adhesion to bovine endothelial cells. Proc. Natl. Acad. Sci. USA. 85, 2800–2804.
Son, H.J., Kim, Y.H., Park, D.I., Kim, J.J., Rhee, P.L., Paik, S.W., Choi, K.W-, Song, S.Y., Rhe, J.C. (2001). Interaction between cyclooxygenase-2 and inducible nitric oxide synthase in gastric cancer. J. Clin. Gastroenterol. 33, 383–388.
Soto-Cerrato, V., Montaner, B., Martinell, M., Vilaseca, M., Giralt, E., and Pérez-Tomás, R. (2005). Cell cycle arrest and proapoptotic effects of the anticancer cyclodepsipeptide serratamolide (AT514) are independent of p53 status in breast cancer cells. Biochem. Pharmacol. 71, 32–41.
Stamler, J.S., Jaraki, O., Osborne, J., Simon, D.I., Keaney, J., Vita, J., Singel, D., Valeri, C.R., and Loscalzo, J. (1992). Nitric oxide circulates in mammalian plasma primarily as an s-nitroso adduct of serum albumin. Proc. Natl. Acad. Sci. USA. 89, 7674–7677.
Stamler, J.S., Lamas, S., and Fang, F.C. (2001). Nitrosylation. the prototypic redox-based signaling mechanism. Cell 106, 675–683.
Stuehr, D.J. and Ikeda-Saito, M. (1992). Spectral characterization of brain and macrophage nitric oxide synthases. Cytochrome P-450-like hemeproteins that contain a flavin semiquinone radical. J. Biol. Chem. 267, 20547–20550.
Szabò, C. (1996). Physiological and pathophysiological roles of nitric oxide in the central nervous system. Brain Res. Bull. 41, 131–141.
Thomsen, L.L., Sargent, J.M, Williamson, C.J., and Elgie, A.W. (1998). Nitric oxide synthase activity in fresh cells from ovarian tumour tissue: relationship of enzyme activity with clinical parameters of patients with ovarian cancer. Biochem. Pharmacol. 56, 1365–1370.
Tsai, A.L., Wei, C., and Kulmacz R.J. (1994). Interaction between nitric oxide and prostaglandin H synthase. Arch. Biochem. Biophys. 313, 367–372.
Upmacis, R.K, Deeb, R.S., and Hajjar, D.P. (1999). Regulation of prostaglandin H2 synthase activity by nitrogen oxides. Biochemistry 38, 12505–12513.
Vallance, P., Collier, J., and Moncada, S. (1989). Nitric oxide synthesised from l-arginine mediates endothelium dependent dilatation in human veins in vivo. Cardiovasc. Res. 23, 1053–1057.
Van der Woude, C.J., Jansen, P.L., Tiebosch, A.T., Beuving, A., Homan, M., Kleibeuker, J.H., and Moshage, H. (2002). Expression of apoptosis-related proteins in Barrett's metaplasia-dysplasia-carcinoma sequence: a switch to a more resistant phenotype. Hum. Pathol. 33, 686–692.
Walia, M., Samson, S.E., Schmidt, T., Best, K., Whittington. M., Kwan, C.Y., and Grover, A.K. (2003). Peroxynitrite and nitric oxide differ in their effects on pig coronary artery smooth muscle. Am. J. Physiol. Cell. Physiol. 284, 649–657.
Wagner, D.A., Young, V.R., and Tannenbaum, S.R. (1983). Mammalian nitrate biosynthesis: incorporation of 15NH3 into nitrate Is enhanced by endotoxin treatment. Proc. Natl. Acad. Sci. USA. 80, 4518–4521.
Weinberg, J.B., Misukonis, M.A., Shami, P.J., Mason, S.N., Sauls, D.L., Dittman, W.A., Wood, E.R., Smith, G.K., McDonald, B., Bachus, K.E., et al. (1995). Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric oxide production by blood monocyte and peritoneal macrophages. Blood 86, 1184–1195.
Whitcomb, D.C. (2004). Inflammation and Cancer V. Chronic pancreatitis and pancreatic cancer. Am. J. Physiol. Gastrointest. Liver Physiol. 287, 315–319.
White, K.A. and Marletta, M.A. (1992). Nitric oxide synthase Is a cytochrome P-450 type hemoprotein. Biochemistry 31, 6627–6631.
Whittle, B.J., Lopez-Belmonte, J., and Rees, D.D. (1989). Modulation of the vasodepressor actions of acetylcholine, bradykinin, substance P and endothelin in the rat by a specific inhibitor of nitric oxide formation. Br. J. Pharmacol. 98, 646–652.
Williams, J.L., Borgo, S., Hasan, I., Castillo, E., Traganos, F., and Rigas. B. (2001). Nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) alter the kinetics of human colon cancer cell lines more effectively than traditional NSAIDs: implications for colon cancer chemoprevention Cancer Res. 61, 3285–3289.
Wink, D.A., Kasprzak, K.S., Maragos, C.M., Elespuru, R.K., Misra, M., Dunams, T.M., Cebula, T.A., Koch, W.H., Andrews, A.W., Allen, J.S. et al. (1991). DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254, 1001–1003.
Wink, D.A. and Mitchell, J. (1998). Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic. Biol. Med. 25, 434–456.
Wu, G.J., Chen, T.G., Chang, H.C., Chiu, W.T., Chang, C.C., and Chen, R.M. (2007). Nitric oxide from both exogenous and endogenous sources activates mitochondria-dependent events and induces insults to human chondrocytes. J. Cell. Biochem. 101, 1520–1531.
Xie, K., Huang, S., Dong, Z., Juang, S.H., Gutman, M., Xie, Q.W., Nathan, C., and Fidler, I.J. (1995). Transfection with the inducible nitric oxide synthase gene suppresses tumorigenicity and abrogates metastasis by K-1735 murine melanoma cells. J. Exp. Med. 181,1333–1343.
Yoshizumi M., Perrella, M.A., Burnett J.C., Jr., and Lee M.E. (1993). Tumor necrosis factor downregulates an endothelial nitric oxide synthase MRNA by shortening its half-life. Circ. Res. 73, 205–209.
Zabel, U., Kleinschnitz, C., Oh, P., Nedvetsky, P., Smolenski, A., Müller, H., Kronich, P., Kugler, P., Walter, U., Schnitzer, J.E., and Schmidt, H.H. (2002). Calcium-dependent membrane association sensitizes soluble guanylyl cyclase to nitric oxide. Nat. Cell. Biol. 4, 307–311.
Zhang, J., Dawson, V.L., Dawson, T.M., and Snyder, S.H. (1994). Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 263, 687–689.
Zingarelli, B., Southan, G.J., Gilad, E., O'Connor, M., Salzman, A. L., and Szabo, C. (1997). The inhibitory effects of mercaptoalkylguanidines on cyclo-oxygenase activity. Br. J. Pharmacol. 120, 357–366.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science + Business Media, LLC
About this chapter
Cite this chapter
Masini, E., Cianchi, F., Mastroianni, R., Cuzzocrea, S. (2010). Nitric Oxide Expression in Cancer. In: Bonavida, B. (eds) Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1432-3_4
Download citation
DOI: https://doi.org/10.1007/978-1-4419-1432-3_4
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-1431-6
Online ISBN: 978-1-4419-1432-3
eBook Packages: MedicineMedicine (R0)