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Erschienen in: Cancer Chemotherapy and Pharmacology 6/2011

01.06.2011 | Mini Review

Nitric oxide: role in tumour biology and iNOS/NO-based anticancer therapies

verfasst von: Simendra Singh, Alok K. Gupta

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 6/2011

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Abstract

Purpose

The diatomic radical nitric oxide (NO) has been the cause of intense debate with implication in carcinogenesis, tumour progression, invasion, angiogenesis and modulation of therapeutic responses. The tumour biology of NO is highly complex, and this review summarises the various protective and damaging mode of action of NO.

Methods

We reviewed all published literature addressing the complexities of the role of NO in the altered biology of cancer and evaluating promising therapeutic roles of NO/iNOS for anti-cancer therapy.

Results

The available experimental evidences highlight contrasting pro- and anti-tumour effects of iNOS expression, which appear to be reconciled by consideration of the concentrations of NO involved, the temporo-spatial mode of NO action, intracellular targets, cellular redox state and the timing of an apoptotic stimulus. Several clinical and experimental studies indicate that the presence of NO in tumour microenvironment is detrimental to tumour cell survival and metastasis. In contrast, numerous reports suggest that NO can have tumour-promoting effects. NO is a ‘double-edged sword’ in cancer, and this review offers insight into the dichotomous nature of NO and discuss the therapeutic gain that can be achieved by manipulating tumour NO.

Conclusions

NO may exert a biphasic response, such that when NO levels go beyond a critical concentration that would be suitable for tumour growth and survival, growth arrest and/or apoptotic pathways are initiated. These characteristics of NO have been exploited therapeutically with impressive effects in pre-clinical models of cancer to slow tumour growth and to enhance the efficacy of both chemotherapy and radiotherapy.
Literatur
1.
Zurück zum Zitat Knowles RG, Moncada S (1994) Nitric oxide synthases in mammals. Biochem J 298:249–258PubMed Knowles RG, Moncada S (1994) Nitric oxide synthases in mammals. Biochem J 298:249–258PubMed
2.
Zurück zum Zitat Nathan C, Xie QW (1994) Regulation of biosynthesis of nitric oxide. J Biol Chem 269:13725–13728PubMed Nathan C, Xie QW (1994) Regulation of biosynthesis of nitric oxide. J Biol Chem 269:13725–13728PubMed
3.
Zurück zum Zitat Elfering SL, Sarkela TM, Giulivi C (2002) Biochemistry of mitochondrial nitric-oxide synthase. J Biol Chem 277:38079–38086PubMedCrossRef Elfering SL, Sarkela TM, Giulivi C (2002) Biochemistry of mitochondrial nitric-oxide synthase. J Biol Chem 277:38079–38086PubMedCrossRef
5.
Zurück zum Zitat Hibbs JBJ (1991) Synthesis of nitric oxide from l-arginine: a recently discovered pathway induced by cytokines with antitumour and antimicrobial activity. Res Immunol 142:565–569PubMedCrossRef Hibbs JBJ (1991) Synthesis of nitric oxide from l-arginine: a recently discovered pathway induced by cytokines with antitumour and antimicrobial activity. Res Immunol 142:565–569PubMedCrossRef
6.
Zurück zum Zitat Kamijo R, Harada H, Matsuyama T, Bosland M, Gerecitano J, Shapiro D, Le J, Koh SI, Kimura T, Green SJ (1994) Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science 263:1612–1615PubMedCrossRef Kamijo R, Harada H, Matsuyama T, Bosland M, Gerecitano J, Shapiro D, Le J, Koh SI, Kimura T, Green SJ (1994) Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science 263:1612–1615PubMedCrossRef
7.
Zurück zum Zitat Tendler DS, Bao C, Wang T, Huang EL, Ratovitski EA, Pardoll DA, Lowenstein CJ (2001) Intersection of interferon and hypoxia signal transduction pathways in nitric oxide-induced tumor apoptosis. Cancer Res 61:3682–3688PubMed Tendler DS, Bao C, Wang T, Huang EL, Ratovitski EA, Pardoll DA, Lowenstein CJ (2001) Intersection of interferon and hypoxia signal transduction pathways in nitric oxide-induced tumor apoptosis. Cancer Res 61:3682–3688PubMed
8.
Zurück zum Zitat Melillo G, Musso T, Sica A, Taylor LS, Cox GW, Varesio LA (1995) Hypoxia responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J Exp Med 182:1683–1693PubMedCrossRef Melillo G, Musso T, Sica A, Taylor LS, Cox GW, Varesio LA (1995) Hypoxia responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J Exp Med 182:1683–1693PubMedCrossRef
9.
Zurück zum Zitat Kepp O, Tesniere A, Zitvogel L, Kroemer G (2008) The immunogenicity of tumor cell death. Curr Op Oncol 21:71–76CrossRef Kepp O, Tesniere A, Zitvogel L, Kroemer G (2008) The immunogenicity of tumor cell death. Curr Op Oncol 21:71–76CrossRef
10.
Zurück zum Zitat Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ (2010) HMGB1 and RAGE in Inflammation and Cancer. Annu Rev Immunol 28:367–388PubMedCrossRef Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ (2010) HMGB1 and RAGE in Inflammation and Cancer. Annu Rev Immunol 28:367–388PubMedCrossRef
11.
Zurück zum Zitat Taguchi A, Blood DC, del Toro G et al (2000) Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature 405:354–360PubMedCrossRef Taguchi A, Blood DC, del Toro G et al (2000) Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature 405:354–360PubMedCrossRef
12.
Zurück zum Zitat Huttunen HJ, Kuja-Panula J, Sorci G et al (2000) Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation. J Biol Chem 275:40096–40105PubMedCrossRef Huttunen HJ, Kuja-Panula J, Sorci G et al (2000) Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation. J Biol Chem 275:40096–40105PubMedCrossRef
13.
Zurück zum Zitat Kuniyasu H, Chihara Y, Kondo H (2003) Differential effects between amphoterin and advanced glycation end products on colon cancer cells. Int J Cancer 104:722–777PubMedCrossRef Kuniyasu H, Chihara Y, Kondo H (2003) Differential effects between amphoterin and advanced glycation end products on colon cancer cells. Int J Cancer 104:722–777PubMedCrossRef
14.
Zurück zum Zitat Thomsen LL, Miles DW, Happerfield L, Bobrow LG, Knowles RG, Moncada S (1995) Nitric oxide synthase activity in human breast cancer. Br J Cancer 72:41–44PubMedCrossRef Thomsen LL, Miles DW, Happerfield L, Bobrow LG, Knowles RG, Moncada S (1995) Nitric oxide synthase activity in human breast cancer. Br J Cancer 72:41–44PubMedCrossRef
15.
Zurück zum Zitat Cobbs CS, Brenman JE, Aldape KD, Bredt DS, Israel MA (1995) Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res 55:727–730PubMed Cobbs CS, Brenman JE, Aldape KD, Bredt DS, Israel MA (1995) Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res 55:727–730PubMed
16.
Zurück zum Zitat Masri FA, Comhair SA, Koeck T, Xu W, Janocha A, Ghosh S, Dweik RA, Golish J, Kinter M, Stuehr DJ, Erzurum SC, Aulak KS (2005) Abnormalities in nitric oxide and its derivatives in lung cancer. Am J Respir Crit Care Med 172:597–605PubMedCrossRef Masri FA, Comhair SA, Koeck T, Xu W, Janocha A, Ghosh S, Dweik RA, Golish J, Kinter M, Stuehr DJ, Erzurum SC, Aulak KS (2005) Abnormalities in nitric oxide and its derivatives in lung cancer. Am J Respir Crit Care Med 172:597–605PubMedCrossRef
17.
Zurück zum Zitat Klotz T, Bloch W, Volberg C, Engelmann U, Addicks K (1998) Selective expression of inducible nitric oxide synthase in human prostate carcinoma. Cancer 82:1897–1903PubMedCrossRef Klotz T, Bloch W, Volberg C, Engelmann U, Addicks K (1998) Selective expression of inducible nitric oxide synthase in human prostate carcinoma. Cancer 82:1897–1903PubMedCrossRef
18.
Zurück zum Zitat Lagares-Garcia JA, Moore RA, Collier B, Heggere M, Diaz F, Qian F (2001) Nitric oxide synthase as a marker in colorectal carcinoma. Am Surg 67:709–713PubMed Lagares-Garcia JA, Moore RA, Collier B, Heggere M, Diaz F, Qian F (2001) Nitric oxide synthase as a marker in colorectal carcinoma. Am Surg 67:709–713PubMed
19.
Zurück zum Zitat Hajri A, Metzger E, Vallat F, Coffy S, Flatter E, Evrard S, Marescaux J, Aprahamian M (1998) Role of nitric oxide in pancreatic tumour growth: in vivo and in vitro studies. Br J Cancer 78:841–849PubMedCrossRef Hajri A, Metzger E, Vallat F, Coffy S, Flatter E, Evrard S, Marescaux J, Aprahamian M (1998) Role of nitric oxide in pancreatic tumour growth: in vivo and in vitro studies. Br J Cancer 78:841–849PubMedCrossRef
20.
Zurück zum Zitat Weninger W, Rendl M, Pammer J, Mildner M, Tschugguel W, Schneeberger C, Stürzl M, Tschachler E (1998) Nitric oxide synthases in Kaposi’s sarcoma are expressed predominantly by vessels and tissue macrophages. Lab Invest 78:949–955PubMed Weninger W, Rendl M, Pammer J, Mildner M, Tschugguel W, Schneeberger C, Stürzl M, Tschachler E (1998) Nitric oxide synthases in Kaposi’s sarcoma are expressed predominantly by vessels and tissue macrophages. Lab Invest 78:949–955PubMed
21.
Zurück zum Zitat Ekmekcioglu S, Ellerhorst J, Smid CM, Prieto VG, Munsell M, Buzaid AC, Grimm EA (2000) Inducible nitric oxide synthase and nitrotyrosine in human metastatic melanoma tumors correlate with poor survival. Clin Cancer Res 6:4768–4775PubMed Ekmekcioglu S, Ellerhorst J, Smid CM, Prieto VG, Munsell M, Buzaid AC, Grimm EA (2000) Inducible nitric oxide synthase and nitrotyrosine in human metastatic melanoma tumors correlate with poor survival. Clin Cancer Res 6:4768–4775PubMed
22.
Zurück zum Zitat Thomsen LL, Lawton FG, Knowles RG, Beesley JE, Riveros-Moreno V, Moncada S (1994) Nitric oxide synthase activity in human gynecological cancer. Cancer Res 54:1352–1354PubMed Thomsen LL, Lawton FG, Knowles RG, Beesley JE, Riveros-Moreno V, Moncada S (1994) Nitric oxide synthase activity in human gynecological cancer. Cancer Res 54:1352–1354PubMed
23.
Zurück zum Zitat Tschugguel W, Pustelnik T, Lass H, Mildner M, Weninger W, Schneeberger C, Jansen B, Tschachler E, Waldhör T, Huber JC, Pehamberger H (1999) Inducible nitric oxide synthase (iNOS) expression may predict distant metastasis in human melanoma. Br J Cancer 79:1609–1612PubMedCrossRef Tschugguel W, Pustelnik T, Lass H, Mildner M, Weninger W, Schneeberger C, Jansen B, Tschachler E, Waldhör T, Huber JC, Pehamberger H (1999) Inducible nitric oxide synthase (iNOS) expression may predict distant metastasis in human melanoma. Br J Cancer 79:1609–1612PubMedCrossRef
24.
Zurück zum Zitat Loibl S, von Minckwitz G, Weber S, Sinn HP, Schini-Kerth VB, Lobysheva I, Nepveu F, Wolf G, Strebhart K, Kufmann M (2002) 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 95:1191–1198PubMedCrossRef Loibl S, von Minckwitz G, Weber S, Sinn HP, Schini-Kerth VB, Lobysheva I, Nepveu F, Wolf G, Strebhart K, Kufmann M (2002) 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 95:1191–1198PubMedCrossRef
25.
Zurück zum Zitat Dudzinski DM, Michel T (2007) Life history of eNOS: partners and pathways. Cardiovascular Res 75:247–260CrossRef Dudzinski DM, Michel T (2007) Life history of eNOS: partners and pathways. Cardiovascular Res 75:247–260CrossRef
26.
Zurück zum Zitat Vakkala M, Paakko P, Soini Y (2000) eNOS expression is associated with the estrogen and progesterone receptor status in invasive breast carcinoma. Int J Oncol 17:667–671PubMed Vakkala M, Paakko P, Soini Y (2000) eNOS expression is associated with the estrogen and progesterone receptor status in invasive breast carcinoma. Int J Oncol 17:667–671PubMed
27.
Zurück zum Zitat Zheng PP, Hop WC, Luider TM et al (2007) Increased levels of circulating endothelial progenitor cells and circulating endothelial nitric oxide synthase in patients with gliomas. Ann Neurol 62:40–48PubMedCrossRef Zheng PP, Hop WC, Luider TM et al (2007) Increased levels of circulating endothelial progenitor cells and circulating endothelial nitric oxide synthase in patients with gliomas. Ann Neurol 62:40–48PubMedCrossRef
28.
Zurück zum Zitat Lim KH, Ancrile BB, Kashatus DF et al (2008) Tumour maintenance is mediated by eNOS. Nature 452:646–649PubMedCrossRef Lim KH, Ancrile BB, Kashatus DF et al (2008) Tumour maintenance is mediated by eNOS. Nature 452:646–649PubMedCrossRef
29.
Zurück zum Zitat Gosink EC, Forsberg EJ (1993) Effects of ATP and bradykinin on endothelial cell Ca2+ homeostasis and formation of cGMP and prostacyclin. Am J Physiol Cell Physiol 265:C1620–C1629 Gosink EC, Forsberg EJ (1993) Effects of ATP and bradykinin on endothelial cell Ca2+ homeostasis and formation of cGMP and prostacyclin. Am J Physiol Cell Physiol 265:C1620–C1629
30.
Zurück zum Zitat Ayajiki K, Kindermann M, Hecker M, Fleming I, Busse R (1996) Intracellular pH and tyrosine phosphorylation but not calcium determine shear stress-induced nitric oxide production in native endothelial cells. Circ Res 78:750–758PubMed Ayajiki K, Kindermann M, Hecker M, Fleming I, Busse R (1996) Intracellular pH and tyrosine phosphorylation but not calcium determine shear stress-induced nitric oxide production in native endothelial cells. Circ Res 78:750–758PubMed
31.
Zurück zum Zitat Wang L, Shi GG, Yao JC et al (2005) Expression of endothelial nitric oxide synthase correlates with the angiogenic phenotype of and predicts poor prognosis in human gastric cancer. Gastric Cancer 8:18–28PubMedCrossRef Wang L, Shi GG, Yao JC et al (2005) Expression of endothelial nitric oxide synthase correlates with the angiogenic phenotype of and predicts poor prognosis in human gastric cancer. Gastric Cancer 8:18–28PubMedCrossRef
32.
Zurück zum Zitat Ariel I, Hochberg A, Shochina M (1998) Endothelial nitric oxide synthase immunoreactivity in early gestation and in trophoblastic disease. J Clin Pathol 51:427–431PubMedCrossRef Ariel I, Hochberg A, Shochina M (1998) Endothelial nitric oxide synthase immunoreactivity in early gestation and in trophoblastic disease. J Clin Pathol 51:427–431PubMedCrossRef
33.
Zurück zum Zitat Bauer PM, Fulton D, Boo YC, Sorescu GP, Kemp BE, Jo H et al (2003) Compensatory phosphorylation and protein–protein interactions revealed by loss of function and gain of function mutants of multiple serine phosphorylation sites in endothelial nitric oxide synthase. J Biol Chem 278:14841–14849PubMedCrossRef Bauer PM, Fulton D, Boo YC, Sorescu GP, Kemp BE, Jo H et al (2003) Compensatory phosphorylation and protein–protein interactions revealed by loss of function and gain of function mutants of multiple serine phosphorylation sites in endothelial nitric oxide synthase. J Biol Chem 278:14841–14849PubMedCrossRef
34.
Zurück zum Zitat Dudzinski DM, Igarashi J, Greif D, Michel T (2006) The regulation and pharmacology of endothelial nitric oxide synthase. Annu Rev Pharmacol Toxicol 46:235–276PubMedCrossRef Dudzinski DM, Igarashi J, Greif D, Michel T (2006) The regulation and pharmacology of endothelial nitric oxide synthase. Annu Rev Pharmacol Toxicol 46:235–276PubMedCrossRef
35.
Zurück zum Zitat Michell BJ, Chen ZZ, Tiganis T, Stapleton D, Katsis F et al (2001) Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem 276:17625–17628PubMedCrossRef Michell BJ, Chen ZZ, Tiganis T, Stapleton D, Katsis F et al (2001) Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem 276:17625–17628PubMedCrossRef
36.
Zurück zum Zitat Duda DG, Fukumura D, Jain RK (2004) Role of eNOS in neovascularization: NO for endothelial progenitor cells. Trends Mol Med 10:143–145PubMedCrossRef Duda DG, Fukumura D, Jain RK (2004) Role of eNOS in neovascularization: NO for endothelial progenitor cells. Trends Mol Med 10:143–145PubMedCrossRef
37.
Zurück zum Zitat Chinje E, Stratford IJ (1997) The role of nitric oxide in growth of solid tumours: a balancing act. Essays Biochem 32:61–72PubMed Chinje E, Stratford IJ (1997) The role of nitric oxide in growth of solid tumours: a balancing act. Essays Biochem 32:61–72PubMed
38.
Zurück zum Zitat Lincoln TM, Dey N, Sellak HH (2001) cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. J Appl Physiol 91:1421–1430PubMed Lincoln TM, Dey N, Sellak HH (2001) cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. J Appl Physiol 91:1421–1430PubMed
39.
Zurück zum Zitat Brunori M, Giuffre A, Forte E, Mastronicola D, Barone MC, Sarti P (2004) Control of cytochrome c oxidase activity by nitric oxide. Biochim Biophys Acta 1655:365–371PubMedCrossRef Brunori M, Giuffre A, Forte E, Mastronicola D, Barone MC, Sarti P (2004) Control of cytochrome c oxidase activity by nitric oxide. Biochim Biophys Acta 1655:365–371PubMedCrossRef
40.
Zurück zum Zitat Thomas DD, Liu X, Kantrow SP, Lancaster JR Jr (2001) The biological lifetime of nitric oxide: implications for the perivascular dynamics of NO and O2. Proc Natl Acad Sci (USA) 98:355–360CrossRef Thomas DD, Liu X, Kantrow SP, Lancaster JR Jr (2001) The biological lifetime of nitric oxide: implications for the perivascular dynamics of NO and O2. Proc Natl Acad Sci (USA) 98:355–360CrossRef
41.
Zurück zum Zitat Cooper CE, Giulivi C (2007) Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology. Am J Physiol Cell Physiol 292:C1993–C2003PubMedCrossRef Cooper CE, Giulivi C (2007) Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology. Am J Physiol Cell Physiol 292:C1993–C2003PubMedCrossRef
42.
Zurück zum Zitat Stuehr DJ, Santolini J, Wang ZQ, Wei CC, Adak S (2004) Update on mechanism and catalytic regulation in the NO synthases. J Biol Chem 279:36167–36170PubMedCrossRef Stuehr DJ, Santolini J, Wang ZQ, Wei CC, Adak S (2004) Update on mechanism and catalytic regulation in the NO synthases. J Biol Chem 279:36167–36170PubMedCrossRef
43.
Zurück zum Zitat Ridnour LA, Thomas DD, Donzelli S, Espey MG, Roberts DD, Wink DA, Isenberg JS (2006) The biphasic nature of nitric oxide responses in tumor biology. Antioxid Red Signal 8:1329–1337CrossRef Ridnour LA, Thomas DD, Donzelli S, Espey MG, Roberts DD, Wink DA, Isenberg JS (2006) The biphasic nature of nitric oxide responses in tumor biology. Antioxid Red Signal 8:1329–1337CrossRef
44.
Zurück zum Zitat Leon L, Jeannin J-F, Bettaieb A (2008) Post-translational modifications induced by nitric oxide (NO): implication in cancer cells apoptosis. Nitric Oxide 19:77–83PubMedCrossRef Leon L, Jeannin J-F, Bettaieb A (2008) Post-translational modifications induced by nitric oxide (NO): implication in cancer cells apoptosis. Nitric Oxide 19:77–83PubMedCrossRef
45.
Zurück zum Zitat Park HS, Yu JW, Cho JH, Kim MS, Huh SH, Ryoo K, Choi EJ (2004) Inhibition of apoptosis signal-regulating kinase 1 by nitric oxide through a thiol redox mechanism. J Biol Chem 279:7584–7590PubMedCrossRef Park HS, Yu JW, Cho JH, Kim MS, Huh SH, Ryoo K, Choi EJ (2004) Inhibition of apoptosis signal-regulating kinase 1 by nitric oxide through a thiol redox mechanism. J Biol Chem 279:7584–7590PubMedCrossRef
46.
Zurück zum Zitat Sumbayev VV (2003) S-nitrosylation of thioredoxin mediates activation of apoptosis signal-regulating kinase 1. Arch Biochem Biophys 415:133–136PubMedCrossRef Sumbayev VV (2003) S-nitrosylation of thioredoxin mediates activation of apoptosis signal-regulating kinase 1. Arch Biochem Biophys 415:133–136PubMedCrossRef
47.
Zurück zum Zitat DelaTorre A, Schroeder RA, Kuo PC (1997) Alteration of NF-kappa B p50 DNA binding kinetics by S-nitrosylation. Biochem Biophy Res Comm 238:703–706CrossRef DelaTorre A, Schroeder RA, Kuo PC (1997) Alteration of NF-kappa B p50 DNA binding kinetics by S-nitrosylation. Biochem Biophy Res Comm 238:703–706CrossRef
48.
Zurück zum Zitat Gopalakrishna R, Chen ZH, Gundimeda U (1993) Nitric oxide and nitric oxide generating agents induce a reversible inactivation of protein kinase C activity and phorbol ester binding. J Biol Chem 268:27180–27185PubMed Gopalakrishna R, Chen ZH, Gundimeda U (1993) Nitric oxide and nitric oxide generating agents induce a reversible inactivation of protein kinase C activity and phorbol ester binding. J Biol Chem 268:27180–27185PubMed
49.
Zurück zum Zitat Park HS, Huh SH, Kim MS, Lee SH, Choi EJ (2000) Nitric oxide negatively regulates c-Jun N-terminal kinase/stress-activated protein kinase by means of S-nitrosylation. Proc Natl Acad Sci 97:14382–14387PubMedCrossRef Park HS, Huh SH, Kim MS, Lee SH, Choi EJ (2000) Nitric oxide negatively regulates c-Jun N-terminal kinase/stress-activated protein kinase by means of S-nitrosylation. Proc Natl Acad Sci 97:14382–14387PubMedCrossRef
50.
Zurück zum Zitat Teng KK, Esposito DK, Schwartz GD, Lander HM, Hempstead BL (1999) Activation of c-Ha-Ras by nitric oxide modulates survival responsiveness in neuronal PC12 cells. J Biol Chem 274:37315–37320PubMedCrossRef Teng KK, Esposito DK, Schwartz GD, Lander HM, Hempstead BL (1999) Activation of c-Ha-Ras by nitric oxide modulates survival responsiveness in neuronal PC12 cells. J Biol Chem 274:37315–37320PubMedCrossRef
51.
Zurück zum Zitat Xu L, Eu JP, Meissner G, Stamler JS (1998) Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279:234–237PubMedCrossRef Xu L, Eu JP, Meissner G, Stamler JS (1998) Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279:234–237PubMedCrossRef
52.
Zurück zum Zitat MacMillan-Crow LA, Greendorfer JS, Vickers SM, Thompson JA (2000) Tyrosine nitration of c-SRC tyrosine kinase in human pancreatic ductal adenocarcinoma. Arch Biochem Biophys 377:350–356PubMedCrossRef MacMillan-Crow LA, Greendorfer JS, Vickers SM, Thompson JA (2000) Tyrosine nitration of c-SRC tyrosine kinase in human pancreatic ductal adenocarcinoma. Arch Biochem Biophys 377:350–356PubMedCrossRef
53.
Zurück zum Zitat West MB, Hill BG, Xuan YT, Bhatnagar A (2006) Protein glutathiolation by nitric oxide: an intracellular mechanism regulating redox protein modification. FASEB J 20:1715–1717PubMedCrossRef West MB, Hill BG, Xuan YT, Bhatnagar A (2006) Protein glutathiolation by nitric oxide: an intracellular mechanism regulating redox protein modification. FASEB J 20:1715–1717PubMedCrossRef
54.
Zurück zum Zitat Maulik D, Ashraf QM, Mishra OP, Delivoria-Papadopoulos M (2008) Activation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) during hypoxia in cerebral cortical nuclei of guinea pig fetus at term: role of nitric oxide. Neurosci Lett 439:94–99PubMedCrossRef Maulik D, Ashraf QM, Mishra OP, Delivoria-Papadopoulos M (2008) Activation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) during hypoxia in cerebral cortical nuclei of guinea pig fetus at term: role of nitric oxide. Neurosci Lett 439:94–99PubMedCrossRef
55.
Zurück zum Zitat Lander HM, Ogiste JS, Pearce SF, Levi R, Novogrodsky A (1995) Nitric oxide stimulated guanine nucleotide exchange on p21ras. J Biol Chem 270:7017–7020PubMedCrossRef Lander HM, Ogiste JS, Pearce SF, Levi R, Novogrodsky A (1995) Nitric oxide stimulated guanine nucleotide exchange on p21ras. J Biol Chem 270:7017–7020PubMedCrossRef
56.
Zurück zum Zitat Duhé RJ, Evans GA, Erwin RA, Kirken RA, Cox GW, Farrar WL (1998) Nitric oxide and thiol redox regulation of Janus kinase activity. Proc Natl Acad Sci 95:126–131PubMedCrossRef Duhé RJ, Evans GA, Erwin RA, Kirken RA, Cox GW, Farrar WL (1998) Nitric oxide and thiol redox regulation of Janus kinase activity. Proc Natl Acad Sci 95:126–131PubMedCrossRef
57.
Zurück zum Zitat Tejedo JR, Cahuana GM, Ramirez R, Esbert M, Jiménez J, Sobrino F, Bedoya FJ (2004) Nitric oxide triggers the phosphatidylinositol 3-kinase/Akt survival pathway in insulin-producing RINm5F cells by arousing Src to activate insulin receptor substrate-1. Endocrinology 145:2319–2327PubMedCrossRef Tejedo JR, Cahuana GM, Ramirez R, Esbert M, Jiménez J, Sobrino F, Bedoya FJ (2004) Nitric oxide triggers the phosphatidylinositol 3-kinase/Akt survival pathway in insulin-producing RINm5F cells by arousing Src to activate insulin receptor substrate-1. Endocrinology 145:2319–2327PubMedCrossRef
58.
Zurück zum Zitat Lander HM, Jacovina AT, Davis RJ, Tauras JM (1996) Differential activation of mitogen-activated protein kinases by nitric oxide-related species. J Biol Chem 271:19705–19709PubMedCrossRef Lander HM, Jacovina AT, Davis RJ, Tauras JM (1996) Differential activation of mitogen-activated protein kinases by nitric oxide-related species. J Biol Chem 271:19705–19709PubMedCrossRef
59.
Zurück zum Zitat Lala PK, Chakraborty C (2001) Role of nitric oxide in carcinogenesis and tumour progression. Lancet Oncol 2:149–156PubMedCrossRef Lala PK, Chakraborty C (2001) Role of nitric oxide in carcinogenesis and tumour progression. Lancet Oncol 2:149–156PubMedCrossRef
60.
Zurück zum Zitat Pervin S, Singh R, Chaudhuri G (2008) Nitric Oide, Nω-hydroxy-l-arginine and breast cancer. Nitric Oxide 19:103–106PubMedCrossRef Pervin S, Singh R, Chaudhuri G (2008) Nitric Oide, Nω-hydroxy-l-arginine and breast cancer. Nitric Oxide 19:103–106PubMedCrossRef
61.
Zurück zum Zitat Thomas DD, Espey MG, Ridnour LA, Hofseth LJ, Mancardi D, Harris CC, Wink DA (2004) Hypoxic inducible factor 1alpha, extracellular signal-regulated kinase, and p53 are regulated by distinct threshold concentrations of nitric oxide. Proc Natl Acad Sci 101:8894–8899PubMedCrossRef Thomas DD, Espey MG, Ridnour LA, Hofseth LJ, Mancardi D, Harris CC, Wink DA (2004) Hypoxic inducible factor 1alpha, extracellular signal-regulated kinase, and p53 are regulated by distinct threshold concentrations of nitric oxide. Proc Natl Acad Sci 101:8894–8899PubMedCrossRef
62.
Zurück zum Zitat Pervin S, Singh R, Hernandez E, Wu G, Chaudhuri G (2007) Nitric oxide in physiologic concentrations targets the translational machinery to increase the proliferation of human breast cancer cells: involvement of mammalian target of rapamycin/eIF4E pathway. Cancer Res 67:289–299PubMedCrossRef Pervin S, Singh R, Hernandez E, Wu G, Chaudhuri G (2007) Nitric oxide in physiologic concentrations targets the translational machinery to increase the proliferation of human breast cancer cells: involvement of mammalian target of rapamycin/eIF4E pathway. Cancer Res 67:289–299PubMedCrossRef
63.
Zurück zum Zitat Schonhoff CM, Gaston B, Mannick JB (2003) Nitrosylation of cytochrome c during apoptosis. J Biol Chem 278:18265–18270PubMedCrossRef Schonhoff CM, Gaston B, Mannick JB (2003) Nitrosylation of cytochrome c during apoptosis. J Biol Chem 278:18265–18270PubMedCrossRef
64.
Zurück zum Zitat Millet A, Bettaieb A, Renaud F, Prevotat L, Hammann A, Solary E, Mignotte B, Jeannin JF (2002) Influence of the nitric oxide donor glyceryl trinitrate on apoptotic pathways in human colon cancer cells. Gastroenterology 123:235–246PubMedCrossRef Millet A, Bettaieb A, Renaud F, Prevotat L, Hammann A, Solary E, Mignotte B, Jeannin JF (2002) Influence of the nitric oxide donor glyceryl trinitrate on apoptotic pathways in human colon cancer cells. Gastroenterology 123:235–246PubMedCrossRef
65.
Zurück zum Zitat Mannick JB, Schonhoff C, Papeta N, Ghafourifar P, Szibor M, Fang K, Gaston B (2001) S-Nitrosylation of mitochondrial caspases. J Cell Biol 154:1111–1116PubMedCrossRef Mannick JB, Schonhoff C, Papeta N, Ghafourifar P, Szibor M, Fang K, Gaston B (2001) S-Nitrosylation of mitochondrial caspases. J Cell Biol 154:1111–1116PubMedCrossRef
66.
Zurück zum Zitat Iyer AKV, Azad N, Wang L, Rojanasakul Y (2008) Role of S-nitrosylation in apoptosis resistance and angiogenesis. Nitric Oxide 19:146–151PubMedCrossRef Iyer AKV, Azad N, Wang L, Rojanasakul Y (2008) Role of S-nitrosylation in apoptosis resistance and angiogenesis. Nitric Oxide 19:146–151PubMedCrossRef
67.
Zurück zum Zitat Cook T, Wang Z, Alber S, Liu K, Watkins SC, Vodovotz Y, Billiar TR, Blumberg D (2004) Nitric oxide and ionizing radiation synergistically promote apoptosis and growth inhibition of cancer by activating p53. Cancer Res 64:8015–8021PubMedCrossRef Cook T, Wang Z, Alber S, Liu K, Watkins SC, Vodovotz Y, Billiar TR, Blumberg D (2004) Nitric oxide and ionizing radiation synergistically promote apoptosis and growth inhibition of cancer by activating p53. Cancer Res 64:8015–8021PubMedCrossRef
68.
Zurück zum Zitat Zhang Y, Xiong Y (2001) A p53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation. Science 292:1910–1915PubMedCrossRef Zhang Y, Xiong Y (2001) A p53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation. Science 292:1910–1915PubMedCrossRef
69.
Zurück zum Zitat Wang X, Zalcenstein A, Oren M (2003) Nitric oxide promotes p53 nuclear retention and sensitizes neuroblastoma cells to apoptosis by ionizing radiation. Cell Death Differ 10:468–476PubMedCrossRef Wang X, Zalcenstein A, Oren M (2003) Nitric oxide promotes p53 nuclear retention and sensitizes neuroblastoma cells to apoptosis by ionizing radiation. Cell Death Differ 10:468–476PubMedCrossRef
70.
Zurück zum Zitat Yakovlev VA, Bayden AS, Graves PR, Kellogg GE, Mikkelsen RB (2010) Nitration of the tumor suppressor protein p53 at tyrosine 327 promotes p53 oligomerization and activation. Biochemistry 49:5331–5339PubMedCrossRef Yakovlev VA, Bayden AS, Graves PR, Kellogg GE, Mikkelsen RB (2010) Nitration of the tumor suppressor protein p53 at tyrosine 327 promotes p53 oligomerization and activation. Biochemistry 49:5331–5339PubMedCrossRef
71.
Zurück zum Zitat Hofseth LJ, Saito S, Hussain SP, Espey MG, Miranda KM, Araki Y, Jhappan C, Higashimoto Y, He P, Linke SP, Quezado MM, Zurer I, Rotter V, Wink DA, Appella E, Harris CC (2003) Nitric oxide-induced cellular stress and p53 activation in chronic inflammation. Proc Natl Acad Sci 1000:143–148CrossRef Hofseth LJ, Saito S, Hussain SP, Espey MG, Miranda KM, Araki Y, Jhappan C, Higashimoto Y, He P, Linke SP, Quezado MM, Zurer I, Rotter V, Wink DA, Appella E, Harris CC (2003) Nitric oxide-induced cellular stress and p53 activation in chronic inflammation. Proc Natl Acad Sci 1000:143–148CrossRef
72.
Zurück zum Zitat Cobbs CS, Samanta M, Harkins LE, Gillespie GY, Merrick BA, MacMillan-Crow LA (2001) Evidence for peroxynitrite-mediated modifications to p53 in human gliomas: possible functional consequences. Arch Biochem Biophys 394:167–172PubMedCrossRef Cobbs CS, Samanta M, Harkins LE, Gillespie GY, Merrick BA, MacMillan-Crow LA (2001) Evidence for peroxynitrite-mediated modifications to p53 in human gliomas: possible functional consequences. Arch Biochem Biophys 394:167–172PubMedCrossRef
73.
Zurück zum Zitat Xu W, Liu L, Smith GC, Charles IG (2000) Nitric oxide upregulates expression of DNA-PKcs to protect cells from DNA-damaging anti-tumour agents. Nat Cell Biol 2:339–345PubMedCrossRef Xu W, Liu L, Smith GC, Charles IG (2000) Nitric oxide upregulates expression of DNA-PKcs to protect cells from DNA-damaging anti-tumour agents. Nat Cell Biol 2:339–345PubMedCrossRef
74.
Zurück zum Zitat Jones MK, Tsugawa K, Tarnawski AS, Baatar D (2004) Dual actions of nitric oxide on angiogenesis: possible roles of PKC, ERK, and AP-1. Biochem Biophys Res Comm 318:520–528PubMedCrossRef Jones MK, Tsugawa K, Tarnawski AS, Baatar D (2004) Dual actions of nitric oxide on angiogenesis: possible roles of PKC, ERK, and AP-1. Biochem Biophys Res Comm 318:520–528PubMedCrossRef
75.
Zurück zum Zitat Pervin S, Singh R, Freije WA, Chaudhuri G (2003) MKP-1-induced dephosphorylation of extracellular signal-regulated kinase is essential for triggering nitric oxide-induced apoptosis in human breast cancer cell lines: implications in breast cancer. Cancer Res 63:8853–8860PubMed Pervin S, Singh R, Freije WA, Chaudhuri G (2003) MKP-1-induced dephosphorylation of extracellular signal-regulated kinase is essential for triggering nitric oxide-induced apoptosis in human breast cancer cell lines: implications in breast cancer. Cancer Res 63:8853–8860PubMed
76.
Zurück zum Zitat Chao JI, Kuo PC, Hsu TS (2004) Down-regulation of survivin in nitric oxide-induced cell growth inhibition and apoptosis of the human lung carcinoma cells. J Biol Chem 279:20267–20276PubMedCrossRef Chao JI, Kuo PC, Hsu TS (2004) Down-regulation of survivin in nitric oxide-induced cell growth inhibition and apoptosis of the human lung carcinoma cells. J Biol Chem 279:20267–20276PubMedCrossRef
77.
Zurück zum Zitat Garbán HJ, Bonavida B (2001) Nitric oxide inhibits the transcription repressor Yin-Yang 1 binding activity at the silencer region of the Fas promoter: a pivotal role for nitric oxide in the up-regulation of Fas gene expression in human tumor cells. J Immunol 167:75–81PubMed Garbán HJ, Bonavida B (2001) Nitric oxide inhibits the transcription repressor Yin-Yang 1 binding activity at the silencer region of the Fas promoter: a pivotal role for nitric oxide in the up-regulation of Fas gene expression in human tumor cells. J Immunol 167:75–81PubMed
78.
Zurück zum Zitat Garbán HJ, Bonavida B (2001) Nitric oxide disrupts H2O2-dependent activation of nuclear factor kappa B. role in sensitization of human tumor cells to tumor necrosis factor-alpha-induced cytotoxicity. J Biol Chem 276:8918–8923PubMedCrossRef Garbán HJ, Bonavida B (2001) Nitric oxide disrupts H2O2-dependent activation of nuclear factor kappa B. role in sensitization of human tumor cells to tumor necrosis factor-alpha-induced cytotoxicity. J Biol Chem 276:8918–8923PubMedCrossRef
79.
Zurück zum Zitat Tozer GM, Prise VE, Chaplin DJ (1997) Inhibition of nitric oxide synthase induces a selective reduction in tumor blood flow that is reversible with l-arginine. Cancer Res 57:948–955PubMed Tozer GM, Prise VE, Chaplin DJ (1997) Inhibition of nitric oxide synthase induces a selective reduction in tumor blood flow that is reversible with l-arginine. Cancer Res 57:948–955PubMed
80.
Zurück zum Zitat Ishii Y, Ogura T, Tatemichi M, Fujisawa H, Otsuka F, Esumi H (2003) Induction of matrix metalloproteinase gene transcription by nitric oxide and mechanisms of MMP-1 gene induction in human melanoma cell lines. Int J Cancer 103:161–168PubMedCrossRef Ishii Y, Ogura T, Tatemichi M, Fujisawa H, Otsuka F, Esumi H (2003) Induction of matrix metalloproteinase gene transcription by nitric oxide and mechanisms of MMP-1 gene induction in human melanoma cell lines. Int J Cancer 103:161–168PubMedCrossRef
81.
Zurück zum Zitat Wu J, Akaike T, Hayashida K, Okamoto T, Okuyama A, Maeda H (2001) Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinases. Jpn J Cancer Res 92:439–451PubMed Wu J, Akaike T, Hayashida K, Okamoto T, Okuyama A, Maeda H (2001) Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinases. Jpn J Cancer Res 92:439–451PubMed
82.
Zurück zum Zitat Aurello P, Rossi Del Monte S, D’Angelo F, Cicchini C, Ciardi A, Bellagamba R, Ravaioli M, Ramacciato G (2009) Vascular endothelial growth factor C and microvessel density in gastric carcinoma: correlation with clinicopathological factors. Our experience and review of the literature. Oncol Res 17:405–411PubMedCrossRef Aurello P, Rossi Del Monte S, D’Angelo F, Cicchini C, Ciardi A, Bellagamba R, Ravaioli M, Ramacciato G (2009) Vascular endothelial growth factor C and microvessel density in gastric carcinoma: correlation with clinicopathological factors. Our experience and review of the literature. Oncol Res 17:405–411PubMedCrossRef
83.
Zurück zum Zitat Nakamura Y, Yasuoka H, Tsujimoto M, Yang Q, Tsukiyama A, Imabun S, Nakahara M, Nakao K, Nakamura M, Mori I, Kakudo K (2003) Clinicopathological significance of vascular endothelial growth factor-C in breast carcinoma with long-term follow-up. Mod Pathol 16:309–314PubMedCrossRef Nakamura Y, Yasuoka H, Tsujimoto M, Yang Q, Tsukiyama A, Imabun S, Nakahara M, Nakao K, Nakamura M, Mori I, Kakudo K (2003) Clinicopathological significance of vascular endothelial growth factor-C in breast carcinoma with long-term follow-up. Mod Pathol 16:309–314PubMedCrossRef
84.
Zurück zum Zitat Ichinoe M, Mikami T, Shiraishi H, Okayasu I (2004) High microvascular density is correlated with high VEGF, iNOS and COX-2 expression in penetrating growth-type early gastric carcinomas. Histopathology 45:612–618PubMedCrossRef Ichinoe M, Mikami T, Shiraishi H, Okayasu I (2004) High microvascular density is correlated with high VEGF, iNOS and COX-2 expression in penetrating growth-type early gastric carcinomas. Histopathology 45:612–618PubMedCrossRef
85.
Zurück zum Zitat Giantonio BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB III (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the eastern cooperative oncology group study E3200. J Clin Oncol 25:1539–1544PubMedCrossRef Giantonio BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB III (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the eastern cooperative oncology group study E3200. J Clin Oncol 25:1539–1544PubMedCrossRef
86.
Zurück zum Zitat Cahlin C, Gelin J, Delbro D, Lönnroth C, Doi C, Lundholm K (2000) Effect of cyclooxygenase and nitric oxide synthase inhibitors on tumor growth in mouse tumor models with and without cancer cachexia related to prostanoids. Cancer Res 60:1742–1749PubMed Cahlin C, Gelin J, Delbro D, Lönnroth C, Doi C, Lundholm K (2000) Effect of cyclooxygenase and nitric oxide synthase inhibitors on tumor growth in mouse tumor models with and without cancer cachexia related to prostanoids. Cancer Res 60:1742–1749PubMed
87.
Zurück zum Zitat Radomski MW, Jenkins DC, Holms L, Moncada S (1991) Human colorectal adenocarcinoma cells: differential nitric oxide synthesis determines their ability to aggregate platelets. Cancer Res 51:6073–6078PubMed Radomski MW, Jenkins DC, Holms L, Moncada S (1991) Human colorectal adenocarcinoma cells: differential nitric oxide synthesis determines their ability to aggregate platelets. Cancer Res 51:6073–6078PubMed
88.
Zurück zum Zitat Dong Z, Staroselsky AH, Qi X, Xie K, Fidler IJ (1994) Inverse correlation between expression of inducible nitric oxide synthase activity and production of metastasis in K-1735 murine melanoma cells. Cancer Res 54:789–793PubMed Dong Z, Staroselsky AH, Qi X, Xie K, Fidler IJ (1994) Inverse correlation between expression of inducible nitric oxide synthase activity and production of metastasis in K-1735 murine melanoma cells. Cancer Res 54:789–793PubMed
89.
Zurück zum Zitat Xie K, Huang S, Dong Z, Juang SH, Gutman M, Xie QW, Nathan C, Fidler IJ (1995) Transfection with the inducible nitric oxide synthase gene suppresses tumorigenicity and abrogates metastasis by K-1735 murine melanoma cells. J Exp Med 181:1333–1343PubMedCrossRef Xie K, Huang S, Dong Z, Juang SH, Gutman M, Xie QW, Nathan C, Fidler IJ (1995) Transfection with the inducible nitric oxide synthase gene suppresses tumorigenicity and abrogates metastasis by K-1735 murine melanoma cells. J Exp Med 181:1333–1343PubMedCrossRef
90.
Zurück zum Zitat Le X, Wei D, Huang S, Lancaster JR Jr, Xie K (2005) Nitric oxide synthase II suppresses the growth and metastasis of human cancer regardless of its upregulation of protumor factors. Proc Natl Acad Sci 102:8758–8763PubMedCrossRef Le X, Wei D, Huang S, Lancaster JR Jr, Xie K (2005) Nitric oxide synthase II suppresses the growth and metastasis of human cancer regardless of its upregulation of protumor factors. Proc Natl Acad Sci 102:8758–8763PubMedCrossRef
91.
Zurück zum Zitat Kiziltepe T, Hideshima T, Ishitsuka K, Ocio EM, Raje N, Catley L, Li C-Q, Trudel LJ, Yasui H, Vallet S, Kutok JL, Chauhan D, Mitsiades CS, Saavedra JE, Wogan GN, Keefer LK, Shami PJ, Anderson KC (2007) JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells. Blood 110:709–718PubMedCrossRef Kiziltepe T, Hideshima T, Ishitsuka K, Ocio EM, Raje N, Catley L, Li C-Q, Trudel LJ, Yasui H, Vallet S, Kutok JL, Chauhan D, Mitsiades CS, Saavedra JE, Wogan GN, Keefer LK, Shami PJ, Anderson KC (2007) JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells. Blood 110:709–718PubMedCrossRef
92.
Zurück zum Zitat Postovit LM, Adams MA, Lash GE, Heaton JP, Graham CH (2004) Nitric oxide-mediated regulation of hypoxia-induced B16F10 melanoma metastasis. Int J Cancer 108:47–53PubMedCrossRef Postovit LM, Adams MA, Lash GE, Heaton JP, Graham CH (2004) Nitric oxide-mediated regulation of hypoxia-induced B16F10 melanoma metastasis. Int J Cancer 108:47–53PubMedCrossRef
93.
Zurück zum Zitat Konovalova NP, Goncharova SA, Volkova LM, Rajewskaya TA, Eremenko LT, Korolev AM (2003) Nitric oxide donor increases the efficiency of cytostatic therapy and reatrds the development of drug resistance. Nitric Oxide 8:59–64PubMedCrossRef Konovalova NP, Goncharova SA, Volkova LM, Rajewskaya TA, Eremenko LT, Korolev AM (2003) Nitric oxide donor increases the efficiency of cytostatic therapy and reatrds the development of drug resistance. Nitric Oxide 8:59–64PubMedCrossRef
94.
Zurück zum Zitat Riganti C, Miraglia E, Viarisio D, Costamagna C, Pescarmona G, Ghigo D, Bosia A (2005) Nitric oxide reverts the resistance to doxorubicin in human colon cancer cells by inhibiting the drug efflux. Cancer Res 65:516–525PubMed Riganti C, Miraglia E, Viarisio D, Costamagna C, Pescarmona G, Ghigo D, Bosia A (2005) Nitric oxide reverts the resistance to doxorubicin in human colon cancer cells by inhibiting the drug efflux. Cancer Res 65:516–525PubMed
95.
Zurück zum Zitat Muir CP, Adams MA, Graham CH (2006) Nitric oxide attenuates resistance to doxorubicin in three-dimensional aggregates of human breast carcinoma cells. Breast Cancer Res Treat 96:169–176PubMedCrossRef Muir CP, Adams MA, Graham CH (2006) Nitric oxide attenuates resistance to doxorubicin in three-dimensional aggregates of human breast carcinoma cells. Breast Cancer Res Treat 96:169–176PubMedCrossRef
96.
Zurück zum Zitat Cook JA, Krishna MC, Pacelli R, DeGraff W, Liebmann J, Mitchell JB, Russo A, Wink DA (1997) Nitric oxide enhancement of melphalan-induced cytotoxicity. Br J Cancer 76:325–334PubMedCrossRef Cook JA, Krishna MC, Pacelli R, DeGraff W, Liebmann J, Mitchell JB, Russo A, Wink DA (1997) Nitric oxide enhancement of melphalan-induced cytotoxicity. Br J Cancer 76:325–334PubMedCrossRef
97.
Zurück zum Zitat Adams DJ, Levesque MC, Weinberg JB, Smith KL, Flowers JL, Moore J, Colvin OM, Silber R (2001) Nitric oxide enhancement of fludarabine cytotoxicity for BCLL lymphocytes. Leukemia 15:1852–1859PubMed Adams DJ, Levesque MC, Weinberg JB, Smith KL, Flowers JL, Moore J, Colvin OM, Silber R (2001) Nitric oxide enhancement of fludarabine cytotoxicity for BCLL lymphocytes. Leukemia 15:1852–1859PubMed
98.
Zurück zum Zitat 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 (2006) 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 24:688–694PubMedCrossRef 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 (2006) 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 24:688–694PubMedCrossRef
99.
Zurück zum Zitat Huang LE, Bindra RS, Glazer PM, Harris AL (2007) Hypoxia-induced genetic instability-a calculated mechanism underlying tumor progression. J Mol Med 85:139–148PubMedCrossRef Huang LE, Bindra RS, Glazer PM, Harris AL (2007) Hypoxia-induced genetic instability-a calculated mechanism underlying tumor progression. J Mol Med 85:139–148PubMedCrossRef
100.
Zurück zum Zitat Brown JM (1999) The hypoxic cell: a target for selective cancer therapy-eighteenth Bruce F. Cain Memorial Award lecture. Cancer Res 59:5863–5870PubMed Brown JM (1999) The hypoxic cell: a target for selective cancer therapy-eighteenth Bruce F. Cain Memorial Award lecture. Cancer Res 59:5863–5870PubMed
101.
Zurück zum Zitat Sandau KB, Fandrey J, Brune B (2001) Accumulation of HIF-1alpha under the influence of nitric oxide. Blood 97:1009–1015PubMedCrossRef Sandau KB, Fandrey J, Brune B (2001) Accumulation of HIF-1alpha under the influence of nitric oxide. Blood 97:1009–1015PubMedCrossRef
102.
Zurück zum Zitat Metzen E, Zhou J, Jelkmann W, Fandrey J, Brune B (2003) Nitric oxide impairs normoxic degradation of HIF-1α by inhibition of prolyl hydroxylases. Mol Biol Cell 14:3470–3481PubMedCrossRef Metzen E, Zhou J, Jelkmann W, Fandrey J, Brune B (2003) Nitric oxide impairs normoxic degradation of HIF-1α by inhibition of prolyl hydroxylases. Mol Biol Cell 14:3470–3481PubMedCrossRef
103.
Zurück zum Zitat Mateo J, Garcia-Lecea M, Cadenas S, Hernandez C, Moncada S (2003) Regulation of hypoxia-inducible factor-1alpha by nitric oxide through mitochondria-dependent and -independent pathways. Biochem J 376:537–544PubMedCrossRef Mateo J, Garcia-Lecea M, Cadenas S, Hernandez C, Moncada S (2003) Regulation of hypoxia-inducible factor-1alpha by nitric oxide through mitochondria-dependent and -independent pathways. Biochem J 376:537–544PubMedCrossRef
104.
Zurück zum Zitat Brown JM, Wilson WR (2004) Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 4:437–447PubMedCrossRef Brown JM, Wilson WR (2004) Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 4:437–447PubMedCrossRef
105.
Zurück zum Zitat McKeown SR, Cowen RL, Williams KJ (2007) Bioreductive drugs: from concept to clinic. Clin Oncol 19:427–442CrossRef McKeown SR, Cowen RL, Williams KJ (2007) Bioreductive drugs: from concept to clinic. Clin Oncol 19:427–442CrossRef
106.
Zurück zum Zitat Peters KB, Brown JM (1993) Tirapazamine: a hypoxia-activated topoisomerase II poison. Cancer Res 62:5248–5253 Peters KB, Brown JM (1993) Tirapazamine: a hypoxia-activated topoisomerase II poison. Cancer Res 62:5248–5253
107.
Zurück zum Zitat Chinje EC, Cowen RL, Feng J, Sharma SP, Wind NS, Harris AL, Stratford IJ (2003) Non-nuclear localized human NOSII enhances the bioactivation and toxicity of tirapazamine (SR4233) in vitro. Mol Pharmacol 63:1248–1255PubMedCrossRef Chinje EC, Cowen RL, Feng J, Sharma SP, Wind NS, Harris AL, Stratford IJ (2003) Non-nuclear localized human NOSII enhances the bioactivation and toxicity of tirapazamine (SR4233) in vitro. Mol Pharmacol 63:1248–1255PubMedCrossRef
108.
Zurück zum Zitat Patterson LH (1993) Rationale for the use of aliphatic N-oxides of cytotoxic anthraquinones as prodrug DNA binding agents: a new class of bioreductive agent. Cancer Metastasis Rev 12:119–134PubMedCrossRef Patterson LH (1993) Rationale for the use of aliphatic N-oxides of cytotoxic anthraquinones as prodrug DNA binding agents: a new class of bioreductive agent. Cancer Metastasis Rev 12:119–134PubMedCrossRef
109.
Zurück zum Zitat Cowen RL, Singh S, Chinje EC, Al-Assah R, Harris P, Dunk C, Stratford IJ (2005) Adenoviral delivery of inducible nitric oxide synthase (NOSII) enhances AQ4 N/radiation cytotoxicity within hypoxic tumor cells. AACR Meeting Abstracts 314-A Cowen RL, Singh S, Chinje EC, Al-Assah R, Harris P, Dunk C, Stratford IJ (2005) Adenoviral delivery of inducible nitric oxide synthase (NOSII) enhances AQ4 N/radiation cytotoxicity within hypoxic tumor cells. AACR Meeting Abstracts 314-A
110.
Zurück zum Zitat Robson T, Worthington J, McKeown SR, Hirst DG (2005) Radiogenic therapy: novel approaches for enhancing tumor radiosensitivity. Technol Cancer Res Treat 4:343–361PubMed Robson T, Worthington J, McKeown SR, Hirst DG (2005) Radiogenic therapy: novel approaches for enhancing tumor radiosensitivity. Technol Cancer Res Treat 4:343–361PubMed
111.
Zurück zum Zitat Gray LH, Green FO, Hawes CA (1958) Effect of nitric oxide on the radiosensitivity of tumour cells. Nature 182:952–953PubMedCrossRef Gray LH, Green FO, Hawes CA (1958) Effect of nitric oxide on the radiosensitivity of tumour cells. Nature 182:952–953PubMedCrossRef
112.
Zurück zum Zitat Mitchell JB, Wink DA, DeGraff W, Gamson J, Keefer LK, Krishna MC (1993) Hypoxic mammalian cell radiosensitization by nitric oxide. Cancer Res 53:5845–5848PubMed Mitchell JB, Wink DA, DeGraff W, Gamson J, Keefer LK, Krishna MC (1993) Hypoxic mammalian cell radiosensitization by nitric oxide. Cancer Res 53:5845–5848PubMed
113.
Zurück zum Zitat Verovski VN, Van den Berge DL, Soete GA, Bols BL, Storme GA (1996) Intrinsic radiosensitivity of human pancreatic tumour cells and the radiosensitising potency of the nitric oxide donor sodium nitroprusside. Br J Cancer 74:1734–1742PubMedCrossRef Verovski VN, Van den Berge DL, Soete GA, Bols BL, Storme GA (1996) Intrinsic radiosensitivity of human pancreatic tumour cells and the radiosensitising potency of the nitric oxide donor sodium nitroprusside. Br J Cancer 74:1734–1742PubMedCrossRef
114.
Zurück zum Zitat Wardman P, Rothkamm K, Folkes LK, Woodcock M, Johnston PJ (2007) Radiosensitization by nitric oxide at low radiation doses. Radiat Res 167:475–484PubMedCrossRef Wardman P, Rothkamm K, Folkes LK, Woodcock M, Johnston PJ (2007) Radiosensitization by nitric oxide at low radiation doses. Radiat Res 167:475–484PubMedCrossRef
115.
Zurück zum Zitat Singh S, Cowen RL, Chinje EC, Stratford IJ (2009) The impact of intracellular generation of nitric oxide on the radiation response of human tumor cells. Radiat Res 171:572–580PubMedCrossRef Singh S, Cowen RL, Chinje EC, Stratford IJ (2009) The impact of intracellular generation of nitric oxide on the radiation response of human tumor cells. Radiat Res 171:572–580PubMedCrossRef
116.
Zurück zum Zitat Li F, Sonveaux P, Rabbani ZN, Liu S, Yan B, Huang Q, Vujaskovic Z, Dewhirst MW, Li CY (2007) Regulation of HIF-1alpha stability through S-nitrosylation. Mol Cell 26:63–74PubMedCrossRef Li F, Sonveaux P, Rabbani ZN, Liu S, Yan B, Huang Q, Vujaskovic Z, Dewhirst MW, Li CY (2007) Regulation of HIF-1alpha stability through S-nitrosylation. Mol Cell 26:63–74PubMedCrossRef
117.
Zurück zum Zitat Abrams J (1992) Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia. Am J Cardiol 70:30B–42BPubMedCrossRef Abrams J (1992) Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia. Am J Cardiol 70:30B–42BPubMedCrossRef
118.
Zurück zum Zitat Soler MN, Bobe P, Benihoud K, Lemaire G, Roos BA, Lausson S (2000) Gene therapy of rat medullary thyroid cancer by naked nitric oxide synthase II DNA injection. J Gene Med 2:344–352PubMedCrossRef Soler MN, Bobe P, Benihoud K, Lemaire G, Roos BA, Lausson S (2000) Gene therapy of rat medullary thyroid cancer by naked nitric oxide synthase II DNA injection. J Gene Med 2:344–352PubMedCrossRef
119.
Zurück zum Zitat Wang Z, Cook T, Alber S, Liu K, Kovesdi I, Watkins SK, Vodovotz Y, Billiar TR, Blumberg D (2004) Adenoviral gene transfer of the human inducible nitric oxide synthase gene enhances the radiation response of human colorectal cancer associated with alterations in tumor vascularity. Cancer Res 64:1386–1395PubMedCrossRef Wang Z, Cook T, Alber S, Liu K, Kovesdi I, Watkins SK, Vodovotz Y, Billiar TR, Blumberg D (2004) Adenoviral gene transfer of the human inducible nitric oxide synthase gene enhances the radiation response of human colorectal cancer associated with alterations in tumor vascularity. Cancer Res 64:1386–1395PubMedCrossRef
120.
Zurück zum Zitat Worthington J, McCarthy HO, Barrett E, Adams C, Robson T, Hirst DG (2004) Use of the radiation-inducible WAF1 promoter to drive iNOS gene therapy as a novel anti-cancer treatment. J Gene Med 6:673–680PubMedCrossRef Worthington J, McCarthy HO, Barrett E, Adams C, Robson T, Hirst DG (2004) Use of the radiation-inducible WAF1 promoter to drive iNOS gene therapy as a novel anti-cancer treatment. J Gene Med 6:673–680PubMedCrossRef
121.
Zurück zum Zitat Halliwill JR, Minson CT, Joyner MJ (2000) Effect of systemic nitric oxide synthase inhibition on postexercise hypotension in humans. J Appl Physiol 89:1830–1836PubMed Halliwill JR, Minson CT, Joyner MJ (2000) Effect of systemic nitric oxide synthase inhibition on postexercise hypotension in humans. J Appl Physiol 89:1830–1836PubMed
122.
Zurück zum Zitat Xu W, Liu LZ, Loizidou M, Ahmed M, Charles IG (2002) The role of nitric oxide in cancer. Cell Res 12:311–320PubMedCrossRef Xu W, Liu LZ, Loizidou M, Ahmed M, Charles IG (2002) The role of nitric oxide in cancer. Cell Res 12:311–320PubMedCrossRef
Metadaten
Titel
Nitric oxide: role in tumour biology and iNOS/NO-based anticancer therapies
verfasst von
Simendra Singh
Alok K. Gupta
Publikationsdatum
01.06.2011
Verlag
Springer-Verlag
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 6/2011
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-011-1654-4

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Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

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