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

Cancer Chemotherapy and Pharmacology

Volumn 67, Issue 6, 2011, Pages 1211-1224

  Singh, Simendra ^a   Gupta, Alok K ^b  

^a SHARDA UNIVERSITY   (India)

^b ETH ZURICH   (Switzerland)

Author keywords

Apoptosis; Bioreductive drugs and gene therapy; Nitric oxide; Nitric oxide synthase; Radiosensitisation

Indexed keywords

1,4 BIS[2 (DIMETHYLAMINO N OXIDE)ETHYLAMINO] 5,8 DIHYDROXYANTHRACENE 9,10 DIONE; 2 O (2,4 DINITROPHENYL) 1 [(4 ETHOXYCARBONYL)PIPERAZIN 1 YL]DIAZEN 1 IUM 1,2 DIOLATE; ANTINEOPLASTIC AGENT; BANOXANTRONE; CYCLIC GMP; CYCLOPHOSPHAMIDE; DOXORUBICIN; FLUDARABINE; INDUCIBLE NITRIC OXIDE SYNTHASE; MELPHALAN; N ACETYL S NITROSOPENICILLAMINE; NITRIC OXIDE; NITRIC OXIDE DONOR; TIRAPAZAMINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER CELL; CANCER CHEMOTHERAPY; CANCER GENE THERAPY; CANCER GROWTH; CANCER INHIBITION; CANCER RADIOTHERAPY; CANCER RESEARCH; CANCER THERAPY; CARCINOGENESIS; CELL SURVIVAL; CONCENTRATION RESPONSE; DRUG TARGETING; HUMAN; LEUKEMIA; METASTASIS; OXIDATION REDUCTION STATE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SHORT SURVEY; TREATMENT RESPONSE;

ANIMALS; CELL HYPOXIA; GENE THERAPY; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; NEOPLASMS; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE II; RADIATION-SENSITIZING AGENTS;

EID: 79959582633     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-011-1654-4     Document Type: Short Survey

References (122)

1. Knowles RG, Moncada S (1994) Nitric oxide synthases in mammals. Biochem J 298:249-258 (Pubitemid 24072462)
2. Nathan C, Xie QW (1994) Regulation of biosynthesis of nitric oxide. J Biol Chem 269:13725-13728 (Pubitemid 24191108)
3. Elfering SL, Sarkela TM, Giulivi C (2002) Biochemistry of mitochondrial nitric-oxide synthase. J Biol Chem 277:38079-38086 (Pubitemid 35154660)
4. Schmidt HH, Walter U (1994) NO at work. Cell 78:919-925 (Pubitemid 24292320)
5. Hibbs JBJ (1991) Synthesis of nitric oxide from L-arginine: a recently discovered pathway induced by cytokines with antitumour and antimicrobial activity. Res Immunol 142:565-569
6. 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 263:1612-1615 (Pubitemid 24128365)
7. 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 61:3682-3688 (Pubitemid 32694980)
8. 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 182:1683-1693
9. Kepp O, Tesniere A, Zitvogel L, Kroemer G (2008) The immunogenicity of tumor cell death. Curr Op Oncol 21:71-76
10. Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ (2010) HMGB1 and RAGE in Inflammation and Cancer. Annu Rev Immunol 28:367-388
11. Taguchi A, Blood DC, del Toro G et al (2000) Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature 405:354-360 (Pubitemid 30337069)
12. 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 275:40096-40105 (Pubitemid 32064635)
13. Kuniyasu H, Chihara Y, Kondo H (2003) Differential effects between amphoterin and advanced glycation end products on colon cancer cells. Int J Cancer 104:722-777
14. Thomsen LL, Miles DW, Happerfield L, Bobrow LG, Knowles RG, Moncada S (1995) Nitric oxide synthase activity in human breast cancer. Br J Cancer 72:41-44
15. Cobbs CS, Brenman JE, Aldape KD, Bredt DS, Israel MA (1995) Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res 55:727-730
16. 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 172:597-605 (Pubitemid 41232971)
17. Klotz T, Bloch W, Volberg C, Engelmann U, Addicks K (1998) Selective expression of inducible nitric oxide synthase in human prostate carcinoma. Cancer 82:1897-1903 (Pubitemid 28208645)
18. 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 67:709-713 (Pubitemid 33739094)
19. 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 78:841-849 (Pubitemid 28430011)
20. 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 78:949-955 (Pubitemid 28378209)
21. 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 6:4768-4775 (Pubitemid 32110418)
22. Thomsen LL, Lawton FG, Knowles RG, Beesley JE, Riveros- Moreno V, Moncada S (1994) Nitric oxide synthase activity in human gynecological cancer. Cancer Res 54:1352-1354 (Pubitemid 24108080)
23. 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 79:1609-1612 (Pubitemid 29116828)
24. 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 95:1191-1198 (Pubitemid 35013051)
25. Dudzinski DM, Michel T (2007) Life history of eNOS: partners and pathways. Cardiovascular Res 75:247-260 (Pubitemid 46961923)
26. 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 17:667-671
27. 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 62:40-48 (Pubitemid 47235279)
28. Lim KH, Ancrile BB, Kashatus DF et al (2008) Tumour maintenance is mediated by eNOS. Nature 452:646-649 (Pubitemid 351483359)
29. 2+ homeostasis and formation of cGMP and prostacyclin. Am J Physiol Cell Physiol 265:C1620-C1629
30. 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 78:750-758 (Pubitemid 26131358)
31. 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 8:18-28 (Pubitemid 40394920)
32. Ariel I, Hochberg A, Shochina M (1998) Endothelial nitric oxide synthase immunoreactivity in early gestation and in trophoblastic disease. J Clin Pathol 51:427-431 (Pubitemid 28312173)
33. 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 278:14841-14849 (Pubitemid 36799811)
34. Dudzinski DM, Igarashi J, Greif D, Michel T (2006) The regulation and pharmacology of endothelial nitric oxide synthase. Annu Rev Pharmacol Toxicol 46:235-276 (Pubitemid 43271190)
35. 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 276:17625-17628
36. Duda DG, Fukumura D, Jain RK (2004) Role of eNOS in neovascularization: NO for endothelial progenitor cells. Trends Mol Med 10:143-145 (Pubitemid 38410970)
37. Chinje E, Stratford IJ (1997) The role of nitric oxide in growth of solid tumours: a balancing act. Essays Biochem 32:61-72 (Pubitemid 127470401)
38. 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 91:1421-1430 (Pubitemid 32803941)
39. 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 1655:365-371 (Pubitemid 38526200)
40. 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) 98:355-360
41. 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-C2003 (Pubitemid 47080509)
42. Stuehr DJ, Santolini J, Wang ZQ, Wei CC, Adak S (2004) Update on mechanism and catalytic regulation in the NO synthases. J Biol Chem 279:36167-36170 (Pubitemid 39128949)
43. 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 8:1329-1337 (Pubitemid 44182431)
44. Leon L, Jeannin J-F, Bettaieb A (2008) Post-translational modifications induced by nitric oxide (NO): implication in cancer cells apoptosis. Nitric Oxide 19:77-83
45. 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 279:7584-7590 (Pubitemid 38294637)
46. Sumbayev VV (2003) S-nitrosylation of thioredoxin mediates activation of apoptosis signal-regulating kinase 1. Arch Biochem Biophys 415:133-136
47. DelaTorre A, Schroeder RA, Kuo PC (1997) Alteration of NF-kappa B p50 DNA binding kinetics by S-nitrosylation. Biochem Biophy Res Comm 238:703-706 (Pubitemid 27472637)
48. 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 268:27180-27185 (Pubitemid 24006436)
49. 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 97:14382-14387 (Pubitemid 32016584)
50. 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 274:37315-37320
51. Xu L, Eu JP, Meissner G, Stamler JS (1998) Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279:234-237 (Pubitemid 28103882)
52. 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 377:350-356
53. West MB, Hill BG, Xuan YT, Bhatnagar A (2006) Protein glutathiolation by nitric oxide: an intracellular mechanism regulating redox protein modification. FASEB J 20:1715-1717
54. 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 439:94-99
55. Lander HM, Ogiste JS, Pearce SF, Levi R, Novogrodsky A (1995) Nitric oxide stimulated guanine nucleotide exchange on p21ras. J Biol Chem 270:7017-7020
56. 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 95:126-131 (Pubitemid 28103918)
57. 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 145:2319-2327 (Pubitemid 38535061)
58. Lander HM, Jacovina AT, Davis RJ, Tauras JM (1996) Differential activation of mitogen-activated protein kinases by nitric oxide-related species. J Biol Chem 271:19705-19709 (Pubitemid 26281705)
59. Lala PK, Chakraborty C (2001) Role of nitric oxide in carcinogenesis and tumour progression. Lancet Oncol 2:149-156 (Pubitemid 33585926)
60. Pervin S, Singh R, Chaudhuri G (2008) Nitric Oide, Nω-hydroxy-L- arginine and breast cancer. Nitric Oxide 19:103-106
61. 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 101:8894-8899 (Pubitemid 38781582)
62. 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 67:289-299 (Pubitemid 46142787)
63. Schonhoff CM, Gaston B, Mannick JB (2003) Nitrosylation of cytochrome c during apoptosis. J Biol Chem 278:18265-18270 (Pubitemid 36799445)
64. 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 123:235-246 (Pubitemid 34747544)
65. Mannick JB, Schonhoff C, Papeta N, Ghafourifar P, Szibor M, Fang K, Gaston B (2001) S-Nitrosylation of mitochondrial caspases. J Cell Biol 154:1111-1116 (Pubitemid 34286189)
66. Iyer AKV, Azad N, Wang L, Rojanasakul Y (2008) Role of S-nitrosylation in apoptosis resistance and angiogenesis. Nitric Oxide 19:146-151
67. 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 64:8015-8021 (Pubitemid 39446937)
68. Zhang Y, Xiong Y (2001) A p53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation. Science 292:1910-1915 (Pubitemid 32538366)
69. 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 10:468-476 (Pubitemid 36626359)
70. 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 49:5331-5339
71. 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 1000:143-148 (Pubitemid 36078042)
72. 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 394:167-172 (Pubitemid 32989325)
73. 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 2:339-345
74. 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 318:520-528 (Pubitemid 38553811)
75. 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 63:8853-8860 (Pubitemid 38064065)
76. 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 279:20267-20276
77. 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 167:75-81 (Pubitemid 32567763)
78. 2-dependent activation of nuclear factor kappa B. role in sensitization of human tumor cells to tumor necrosis factoralpha-induced cytotoxicity. J Biol Chem 276:8918-8923
79. 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 57:948-955 (Pubitemid 27098023)
80. 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 103:161-168 (Pubitemid 35461507)
81. 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 92:439-451 (Pubitemid 32427781)
82. 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 17:405-411
83. 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 16:309-314 (Pubitemid 36443979)
84. 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 45:612-618 (Pubitemid 40029821)
85. 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 25:1539-1544 (Pubitemid 46733080)
86. 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 60:1742-1749 (Pubitemid 30183450)
87. 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 51:6073-6078
88. 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 54:789-793 (Pubitemid 24068338)
89. 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 181:1333-1343
90. 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 102:8758-8763 (Pubitemid 40862808)
91. 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 110:709-718 (Pubitemid 47105410)
92. Postovit LM, Adams MA, Lash GE, Heaton JP, Graham CH (2004) Nitric oxide-mediated regulation of hypoxia-induced B16F10 melanoma metastasis. Int J Cancer 108:47-53 (Pubitemid 37444442)
93. 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 8:59-64 (Pubitemid 36263433)
94. 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 65:516-525
95. 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 96:169-176
96. 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 76:325-334 (Pubitemid 27308082)
97. 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 15:1852-1859 (Pubitemid 33114991)
98. 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 24:688-694 (Pubitemid 46630435)
99. Huang LE, Bindra RS, Glazer PM, Harris AL (2007) Hypoxia-induced genetic instability-a calculated mechanism underlying tumor progression. J Mol Med 85:139-148 (Pubitemid 46188219)
100. Brown JM (1999) The hypoxic cell: a target for selective cancer therapy-eighteenth Bruce F. Cain Memorial Award lecture. Cancer Res 59:5863-5870
101. Sandau KB, Fandrey J, Brune B (2001) Accumulation of HIF-1alpha under the influence of nitric oxide. Blood 97:1009-1015 (Pubitemid 32154286)
102. 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 14:3470-3481 (Pubitemid 37013142)
103. 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 376:537-544 (Pubitemid 38010539)
104. Brown JM, Wilson WR (2004) Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 4:437-447 (Pubitemid 38745529)
105. McKeown SR, Cowen RL, Williams KJ (2007) Bioreductive drugs: from concept to clinic. Clin Oncol 19:427-442 (Pubitemid 46995614)
106. Peters KB, Brown JM (1993) Tirapazamine: a hypoxia-activated topoisomerase II poison. Cancer Res 62:5248-5253
107. 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 63:1248-1255 (Pubitemid 36627219)
108. 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 12:119-134
109. 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. Robson T, Worthington J, McKeown SR, Hirst DG (2005) Radiogenic therapy: novel approaches for enhancing tumor radiosensitivity. Technol Cancer Res Treat 4:343-361 (Pubitemid 41242610)
111. Gray LH, Green FO, Hawes CA (1958) Effect of nitric oxide on the radiosensitivity of tumour cells. Nature 182:952-953
112. Mitchell JB, Wink DA, DeGraff W, Gamson J, Keefer LK, Krishna MC (1993) Hypoxic mammalian cell radiosensitization by nitric oxide. Cancer Res 53:5845-5848 (Pubitemid 24006145)
113. 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 74:1734-1742 (Pubitemid 26401892)
114. Wardman P, Rothkamm K, Folkes LK, Woodcock M, Johnston PJ (2007) Radiosensitization by nitric oxide at low radiation doses. Radiat Res 167:475-484 (Pubitemid 351292978)
115. 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 171:572-580
116. 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 26:63-74 (Pubitemid 46550936)
117. Abrams J (1992) Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia. Am J Cardiol 70:30B-42B
118. 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 2:344-352
119. 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 64:1386-1395 (Pubitemid 38235607)
120. 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 6:673-680 (Pubitemid 40228083)
121. Halliwill JR, Minson CT, Joyner MJ (2000) Effect of systemic nitric oxide synthase inhibition on postexercise hypotension in humans. J Appl Physiol 89:1830-1836
122. Xu W, Liu LZ, Loizidou M, Ahmed M, Charles IG (2002) The role of nitric oxide in cancer. Cell Res 12:311-320 (Pubitemid 135708343)