Skip to main content
SpringerLink
Log in

Nitric Oxide Expression in Cancer

  • Chapter
  • First Online:
Nitric Oxide (NO) and Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 1062 Accesses

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Altieri, D.C. (2008a). New wirings in the survivin networks. Oncogene 27, 6276–6284.

    Article  PubMed  CAS  Google Scholar 

  • Altieri, D.C. (2008b). Survivin, cancer networks and pathway-directed drug discovery. Nat. Rev. Cancer. 8, 61–70.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Butler, A.R. and Williams, D.L.H. (1993). The physiological role of nitric oxide. Chem. Soc. Reviews 1, 233–241.

    Article  Google Scholar 

  • Calver, A., Collier, J., and Vallance, P. (1993). Nitric oxide and cardiovascular control. Exp. Physiol. 78, 303–326.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Chiou, G.C. (2001). Review: effects of nitric oxide on eye diseases and their treatment. J. Ocul. Pharmacol. Ther. 17, 189–198.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Fukumura, D., Kashiwagi, S., and Jain, R.K. (2006). The role of nitric oxide in tumour progression. Nat. Rev. Cancer 6, 521–534.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Garthwaite, G., and Garthwaite, J. (1991). Mechanisms of AMPA neurotoxicity in rat brain slices. Eur. J. Neurosci. 3, 729–736.

    Google Scholar 

  • Garthwaite, J. and Boulton, C.L. (1995). Nitric oxide signaling in the central nervous system. Annu. Rev. Physiol. 57, 683–706.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Ischiropoulos, H., Zhu, L., and Beckman, J.S. (1992). Peroxynitrite formation From macrophage-derived nitric oxide. Arch. Biochem. Biophys. 298, 446–451.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Knowles, R.G. and Moncada, S. (1994). Nitric oxide synthases in mammals. Biochem. J. 298, 249–258.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Millan, A. and Huerta, S. (2009). Apoptosis-inducing factor and colon cancer. J. Surg. Res. 151, 163–170.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Nathan, C. (1992). Nitric Oxide As a Secretory Product of Mammalian Cells. FASEB J. 6, 3051–3064.

    PubMed  CAS  Google Scholar 

  • Nathan, C. and Xie, Q.W. (1994). Nitric oxide synthases: roles, tolls, and controls. Cell 78: 915–918.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Rao, C.V. (2004). Nitric oxide signaling in colon cancer chemoprevention. Mutat. Res. 555, 107–119.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Sessa, W.C. (2004). eNOS at a glance. J. Cell. Sci. 117, 2427–2429.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Simmons, M.L. and Murphy, S. (1994). Roles for protein kinases in the induction of nitric oxide synthase in astrocytes. Glia. 11, 227–234.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Stamler, J.S., Lamas, S., and Fang, F.C. (2001). Nitrosylation. the prototypic redox-based signaling mechanism. Cell 106, 675–683.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Szabò, C. (1996). Physiological and pathophysiological roles of nitric oxide in the central nervous system. Brain Res. Bull. 41, 131–141.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Tsai, A.L., Wei, C., and Kulmacz R.J. (1994). Interaction between nitric oxide and prostaglandin H synthase. Arch. Biochem. Biophys. 313, 367–372.

    Article  PubMed  CAS  Google Scholar 

  • Upmacis, R.K, Deeb, R.S., and Hajjar, D.P. (1999). Regulation of prostaglandin H2 synthase activity by nitrogen oxides. Biochemistry 38, 12505–12513.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Whitcomb, D.C. (2004). Inflammation and Cancer V. Chronic pancreatitis and pancreatic cancer. Am. J. Physiol. Gastrointest. Liver Physiol. 287, 315–319.

    Article  Google Scholar 

  • White, K.A. and Marletta, M.A. (1992). Nitric oxide synthase Is a cytochrome P-450 type hemoprotein. Biochemistry 31, 6627–6631.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy

    Emanuela Masini & Rosanna Mastroianni

  2. Department of General Surgery, Medical School, University of Florence, Florence, Italy

    Fabio Cianchi

  3. Institute of Pharmacology, University of Messina, Messina, Italy

    Salvatore Cuzzocrea

Authors
  1. Emanuela Masini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fabio Cianchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rosanna Mastroianni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Salvatore Cuzzocrea
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emanuela Masini .

Editor information

Editors and Affiliations

  1. Dept. Microbiology, Immunology &, Molecular Genetics, University of California, Los Angeles, Charles E. Young Dr. E. 609, Los Angeles, 90095, California, USA

    Benjamin Bonavida

Rights and permissions

Reprints 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)

Publish with us

Policies and ethics

Search

Navigation