Targeting the L-arginine-nitric oxide pathway for cancer treatment

Current Pharmaceutical Design

Volumn 16, Issue 4, 2010, Pages 392-410

  Ma, Qingyong ^a   Wang, Zheng ^a   Zhang, Min ^a   Hu, Hengtong ^a   Li, Junhui ^a   Zhang, Dong ^a   Guo, Kun ^a   Sha, Huanchen ^a  

^a XI'AN JIAOTONG UNIVERSITY   (China)

Author keywords

Cancer therapy; Cell apoptosis; Cell proliferation; L arginine; Metastasis; Nitric oxide; Nitric oxide synthase; Tumor

Indexed keywords

3,3 BIS(2 AMINOETHYL) 1 HYDROXY 2 OXOTRIAZENE; ARGININE; CISPLATIN; CURCUMIN; EBSELEN; ENDOTHELIAL NITRIC OXIDE SYNTHASE; FENRETINIDE; GLYCERYL TRINITRATE; INDUCIBLE NITRIC OXIDE SYNTHASE; ISOSORBIDE DINITRATE; ISOSORBIDE MONONITRATE; N(G) NITROARGININE METHYL ESTER; NAVELBINE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE;

ANGIOGENESIS; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER GROWTH; CANCER THERAPY; CELL PROLIFERATION; HUMAN; IONIZING RADIATION; LUNG NON SMALL CELL CANCER; METASTASIS; NONHUMAN; PRIORITY JOURNAL; RADIOSENSITIVITY; REVIEW; SIGNAL TRANSDUCTION; AGONISTS; ANIMAL; ANTAGONISTS AND INHIBITORS; GENETICS; METABOLISM; NEOPLASMS; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY; VASCULARIZATION;

ANIMALS; ARGININE; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; NITRIC OXIDE; NITRIC OXIDE SYNTHASE;

EID: 77949442081     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161210790232121     Document Type: Review

References (261)

1. Wu G, Morris Jr SM. Arginine metabolism; nitric oxide and beyond. Biochem J 1998; 336: 1-17.
2. Wu G, Meininger C, Knabe DA, Bazer FW, Rhoads JM. Arginine nutrition in development, health and disease. Curr Opin Clin Nutr Metab Care 2000; 3: 59-66.
3. Gianotti L, Braga M, Nespoli L, Radaelli G, Beneduce A, Di Carlo V. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 2002; 122: 1763-70.
4. Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. J Am Med Assoc 2001; 286: 944-53.
5. Bronte V, Zanovello P. Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 2005; 5: 641-54.
6. Moncada S, Higgs A. The L-Arginine-nitric oxide pathway. N Engl J Med 1993; 329: 2002-12.
7. Becker T, Mevius I, de Vries DK, Schaapherder AF, zu Vilsendorf AM, Klempnauer J, et al. The L-arginine/NO pathway in end-stage liver disease and during orthotopic liver and kidney transplantation: biological and analytical ramifications. Nitric Oxide 2009; 20: 61-7.
8. Park IS, Kang SW, Shin YJ, Chae KY, Park MO, Kim MY, et al. Arginine deminase: a potentia linhibitor of angiogenesis and tumor growth. Br J Cancer 2003; 89: 907-14.
9. Izzo F, Marra P, Beneduce G, Castello G, Vallone P, DeRosa V, et al. Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from PhaseI/II studies. J Clin Oncol 2004; 22: 1815-22.
10. Wheatley DN, Campbell E. Arginine catabolism, liver extracts and cancer. Pathol Oncol Res 2002; 8: 18-25.
11. CaoY. Tumor angiogenesis and therapy. Biomed Pharmacother 2005; 59: S340-3.
12. Harper J, Moses MA. Molecular regulation of tumor angiogenesis: mechanisms and therapeutic implicaions. Exp Suppl 2006; 98: 223-68.
13. Hahnfeldt P, Panigrahy D, Folkman J, Hlatky L. Tumor development under angiogenic signaling: a dynamical heoryof tumorgrowth, treatment response, andpost- vascular dormancy. Cancer Res 1999; 59: 4770-5.
14. Folkman J. Angiogenesis. Annu Rev Med 2006; 57: 1-18.
15. Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002; 29: 15-8.
16. Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks umor angiogenesis and growth. Nat Med 2001; 7: 1194-201.
17. Bagley RG, Weber W, Rouleau C, Teicher BA. Pericytes and endothelial precursor cells: cellular interactions and contributions to malignancy. Cancer Res 2005; 65: 9741-50.
18. Bagley RG, Walter-Yohrling J, Cao X, Weber W, Simons B, Cook BP, et al. Endothelial precursor cells as a model of tumor endothelium: characterization and comparison with mature endothelial cells. Cancer Res 2003; 63: 5866-73.
19. Morbidelli L, Donnini S, Ziche M. Role of nitric oxide in the modulation of angiogenesis. Curr Pharm Des 2003; 9: 521-30.
20. Fulton D, Gratton JP, SessaWC. Post-translational control of endothelial nitric oxide synthase: why isn't calcium/calmodulin enough? J Pharmacol Exp Ther 2001; 299: 818-24.
21. Duda DG, Fukumura D, Jain RK. Role of eNOS in neovascularization: NO for endothelial progenitor cells. Trends Mol Med 2004; 10: 143-5.
22. Isenberg JS, Ridnour LA, Perruccio EM, EspeyMG, Wink DA, Roberts DD. Thrombospondin-1inhibits endothelial cell responses to nitric oxide in a cGMP-dependent manner. Proc Natl Acad Sci USA 2005; 102: 13141-6.
23. Ridnour LA, Isenberg JS, Espey MG, Thomas DD, Roberts DD, Wink DA. Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1. Proc Natl Acad Sci USA 2005; 102: 13147-52.
24. Ignarro LJ. Endothelium-derived nitric oxide: actions and properties. FASEB J 1989; 3: 31-6.
25. Hofseth LJ, Hussain SP, Wogan GN, Harris CC. Nitric oxide in cancer and chemoprevention. Free Radic Biol Med 2003; 34: 955-68.
26. Chen JX, Lawrence ML, Cunningham G, Christman BW, Meyrick B. HSP90 and Akt modulate Ang-1-induced angiogenesis via NO in coronary artery endothelium. J Appl Physiol 2004; 96: 612-20.
27. Bucci M, Roviezzo F, Cicala C, Pinto A, Cirino G. 17-beta-oestradiol- induced vasorelaxation in vitro is mediated bye NOS throughh sp90 and akt/pkb dependent mechanism. Br J Pharmacol 2002; 135: 1695-700.
28. Fontana J, Fulton D, Chen Y, Fairchild TA, McCabe TJ, Fujita N, et al. Domain mapping studies reveal that theMdomain of hsp90 serves as a molecular scaffold to regulate Akt-dependent phosphorylation of endothelial nitric oxide synthase and NO release. Circ Res 2002; 90: 866-73.
29. Robert DD, Isenberg JS, Ridnour LA, Wink DA. Nitric oxide and its gatekeeper thrombospondin-1 in tumorangiogenesis. Clin Cancer Res 2007; 13: 795-98.
30. Schroeder RA, Gu JS, Kuo PC. Interleukin-1beta-stimulated production of nitric oxide in rat hepatocytes is mediated through endogenous synthesis of interferon gamma. Hepatology 1998; 27: 711-9.
31. Kleinert H, Wallerath, T, Fritz G, Ihrig-Biedert I, Rodriguez-Pascual F, Geller DA, et al. Cytokine induction of NO synthase II in human DLD-1 cells: roles of the JAK-STAT, AP-1 and NF-kappaB signaling pathways. Br J Pharmacol 1998; 125: 193-201.
32. Ganster RW, Taylor BS, Shao L, Geller DA. Complex regulation of human inducible nitric oxide synthase gene transcription by stat 1 and NF-kappaB. Proc Nat Acad Sci USA 2001; 98: 8638-43.
33. Lee JK, Choi SS, Won JS, Suh HW. The regulation of inducible nitric oxide synthase gene expression induced by lipopolysaccharide and tumor necrosis factor-alpha in C6 cells: Involvement of AP-1 And NF-kappaB. Life Sci 2003; 73: 595-609.
34. Singh K, Balligand JL, Fischer TA, Smith TW, Kelly RA. Regulation of cytokine-inducible nitric oxide synthase in cardiac myocytes and microvascular endothelial cells: role of extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) and STAT1 alpha. J Biol Chem 1996; 271: 1111-7.
35. Kristof, AS, Marks-Konczalik J, Moss J. Mitogen-activated protein kinases mediate activator protein-1-dependent human inducible nitric-oxide synthase promoter activation. J Biol Chem 2001; 276: 8445-52.
36. Palmer LA, Semenza GL, Stoler MH, Johns RA. Hypoxia induces type II NOS gene expression in pulmonary artery endothelial cells via HIF-1. Am J Physiol 1998; 274: L212-9.
37. Karin M. Nuclear factor-kappaB in cancer development and progression. Nature 2006; 441: 431-6.
38. Ni Z, Lou W, Leman ES, Gao AC. Inhibition of constitutively activated STAT3 signaling pathway suppresses growth of prostate cancer cells. Cancer Res 2000; 60: 1225-28.
39. Yu H, Jove R. The STATs of cancer - new molecular targets come of age. Nat Rev Cancer 2004; 4: 97-105.
40. Shuai K, Liu B. Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol 2003; 3: 900-11.
41. Chang WC, Lee YC, Liu CL, Hsu JD, Wang HC, Chen CC, et al. Increased expression of iNOS and C-Fos via regulation of protein tyrosine phosphorylation and MEK1/ERK2 proteins in terminal bronchiole lesions in the lungs of rats exposed to cigarette smoke. Arch Toxicol 2001; 75: 28-3.
42. Xu X, Malave A. p38 MAPK, but not p42/p44 MAPK mediated inducible nitric oxide synthase expression in C6 glioma cells. Life Sci 2000; 67: 3221-30.
43. Zi X, Agarwal R. Odulation of mitogen-activated protein kinase activation and cell cycle regulators by the potent skin cancer preventive agent silymarin. Biochem Biophys Res Commun 1999; 263: 528-36.
44. Manson MM. Inhibition of survival signalling by dietary polyphenols and indole-3-carbinol. Eur J Cancer 2005; 41: 1842-53.
45. Xu W, Liu LZ, Loizidou M, Ahmed M, Charles IG. The role of nitric oxide in cancer. Cell Res 2002; 12: 311-20.
46. Morbidelli L, Donnini S, Ziche M. Role of nitric oxide in tumor angiogenesis. Cancer Treat Res 2004; 117: 155-67.
47. Liu CY, Wang CH, Chen TC, Lin HC, Yu CT, Kuo HP. Increased level of exhaled nitric oxide and up-regulation of inducible nitric oxide synthase in patients with primary lung cancer. Br J Cancer 1998; 78: 534-41.
48. Kawasaki K, Smith RS Jr, Hsieh CM, Sun J, Chao J, Liao JK. Activation of the phosphatidylinositol 3-kinase/protein kinase Akt pathway mediates nitric oxide-induced endothelial cell migration and angiogenesis. Mol Cell Biol 2003; 23: 5726-37.
49. Fukumura D. Jain RK. Role of nitric oxide in angiogenesis and microcirculation in tumors. Cancer Metastasis Rev 1998; 17: 77-89.
50. Papapetropoulos A, Garcia-Cardena G, Madri JA, Sessa WC. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 1997; 100: 3131-39.
51. Maulik N, Das DK. Redox signaling in vascular angiogenesis. Free Radic Biol Med 2002; 33: 1047-60.
52. Zhang J, Peng B, Chen X. Expressions of nuclear factor κB, inducible nitric oxide synthase, and vascular endothelial growth factor in adenoid cystic carcinoma of salivary glands: correlations with the angiogenesis and clinical outcome. Clin Cancer Res 2005; 11: 7334-43.
53. Chin K, Kurashima Y, Ogura T, Tajiri H, Yoshida S, Esumi H. Induction of vascular endothelial growth factor by nitric oxide in human glioblastoma and hepatocellular carcinoma cells. Oncogene 1997; 15: 437-42.
54. Kimura H, Weisz A, Kurashima Y, Hashimoto K, Ogura T, D'Acquisto F, et al. Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor-1 activity by nitric oxide. Blood 2000; 95: 189-97.
55. Sandau KB, Zhou J, Kietzmann T, Brune B. Regulation of the hypoxia-inducible factor 1α by the inflammatory mediators nitric oxide and tumor necrosis factor-α in contrast to desferroxamine and phenylarsine oxide. J Biol Chem 2001; 276: 39805-11.
56. Talks KL, Turley H, Gatter KC, Maxwell PH, Pugh CW, Ratcliffe PJ, et al. Expression and distribution of the hypoxia inducible factors HIF-1α and HIF-2α in normal human tissues, cancers, and tumor- associated macrophages. Am J Pathol 2002; 157: 411-21.
57. Hockel M, Schlenger K, Hockel S, Vaupel P. Hypoxic cervical cancers with low apoptotic index are highly aggressive. Cancer Res 1999; 59: 4525-8.
58. Harris AL. Hypoxia-a key regulatory factor in tumor growth. Nature 2000; 2: 38-47.
59. Yin MB, Li ZR, Toth K, Cao S, Durrani FA, Hapke G, et al. Potentiation of irinotecan sensitivity by se-methylselenocysteine in an in vivo tumor model is associated with down-regulation of cyclooxygenase-2, inducible nitric oxide synthase, and hypoxiainducible factor 1alpha expression, resulting in reduced angiogenesis. Oncogene 2006; 25: 2509-19.
60. Jun Yu, deMuinck ED, Zhuang Z, Drinane M, Kauser K, Rubanyi GM, et al. Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve. Proc Natl Acad Sci USA 2005; 102: 10999-1004.
61. Kasuno K. Nitric oxide induces hypoxia-inducible factor 1 activation that is dependent on MAPK and phosphatidylinositol 3-kinase signaling. J Biol Chem 2004; 279: 2550-8 .
62. Sogawa K. Inhibition of hypoxia-inducible factor 1 activity by nitric oxide donors in hypoxia. Proc Natl Acad Sci USA 1998; 95: 7368-73.
63. Huang LE, Willmore WG, Gu J, Goldberg MA, Bunn HF. Inhibition of hypoxia-inducible factor 1 activation by carbon monoxide and nitric oxide. implications for oxygen sensing and signaling. J Biol Chem 1999; 274: 9038-44.
64. Liu Y. Carbon monoxide and nitric oxide suppress the hypoxic induction of vascular endothelial growth factor gene via the 5′ enhancer. J Biol Chem 1998; 273: 15257-62.
65. Metzen E, Zhou J, Jelkmann W, Fandrey J, Brune B. Nitric oxide impairs normoxic degradation of HIF-1α by inhibition of prolyl hydroxylases. Mol Biol Cell 2003; 14: 3470-81.
66. Brüne B, Zhou J. Nitric oxide and superoxide: Interference with hypoxic signaling. Cardiovasc Res 2007; 75: 275-82.
67. Roberts DD. Regulation of tumor growth and meastasis by thrombospondin-1. FASEB J 1996; 10: 1183-91.
68. Lawler J. Thrombospondin-1 as an endogenous inhibitor of angiogenesis and tumor growth. J Cell Mol Med 2002; 6: 1-12.
69. Lawler J, Detmar M. Tumor progression: the effects of thrombospondin-1and -2. Int J Biochem Cell Biol 2004; 36: 1038-45.
70. Chen H, Herndon ME, Lawler J. The cell biology of thrombospondin-1. Matrix Biol 2000; 19: 597-614.
71. Calzada MJ, Roberts DD. Novel integrin antagonists derived from thrombospondins. Curr Pharm Des 2005; 11: 849-66.
72. Fukumura D, Kashiwagi S, Jai RK. The role of nitric oxide in tumor progression. Nat Rev Cancer 2006; 6: 251-34.
73. Marcet-Palacios M. Nitric oxide and cyclic GMP increase the expression of matrix metalloproteinase-9 in vascular smooth muscle. J Pharmacol Exp Ther 2003; 307: 429-36.
74. Gu Z. S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science 2002; 297: 1186-90.
75. Rafii S, Lyden D, Benezra R, Hattori K, Heissig B. Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nat Rev Cancer 2002; 2: 826-35.
76. Jain RK. Molecular regulation of vessel maturation. Nat Med 2003; 9: 685-93.
77. Kashiwagi S. NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels. J Clin Invest 2005; 115: 1816-27.
78. Pervin S, Singh R, Chaudhuri G. Nitric oxideinduced cytostasis and cell cycle arrest of a human breast cancer cell line (MDA-MB-231): potential role of cyclin D1. Proc Natl Acad Sci USA 2001; 98: 3583-8.
79. Ruano MJ, Herna' ndez-Hernando S, Jiménez A, Estrada C, Villalobo A. Nitric oxide-induced epidermal growth factor-dependent phosphorylations in A431 tumor cells. Eur J Biochem 2003; 270: 1828-37.
80. Ciani E, Severi S, Contestabile A, Bartesaghi R, Contestabile A. Nitric oxide negatively regulates proliferation and promotes neuronal differentiation through N-Myc downregulation. J Cell Sci 2004; 117: 4727-37.
81. Murillo-Carretero M, Ruano MJ, Rodr' guez-Matarredona E, Villalobo A, Estrada C. Antiproliferative effect of nitric oxide on epidermal growth factor-responsive human neuroblastoma cells. J Neurochem 2002; 83: 119-31.
82. Estrada C, Gomez C, Martin-Nieto J, De Frutos T, Jimé nez A, Villalobo A. Nitric oxide reversibly inhibits the epidermal growth factor receptor tyrosine kinase. Biochem J 1997; 326: 369-76.
83. Bal-Price A, Gartlon J, Brown GC. Nitric oxide stimulates PC12 cell proliferation via cGMP and inhibits at higher concentrations mainly via energy depletion. Nitric Oxide 2006; 14: 238-46.
84. Tesei A, Ricotti L, Ulivi P, Medri L, Amadori D, Zoli W. NCX 4016, a nitric oxide-releasing aspirin derivative, exhibits a significant antiproliferative effect and alters cell cycle progression in human colon adenocarcinoma cell lines. Int J Oncol 2003; 22: 1297-1302.
85. Buga GM, Wei LH, Bauer PM, Fukuto JM, Ignarro LJ. NG-hydroxy-l-arginine and nitric oxide inhibit Caco-2 tumor cell proliferation by distinct mechanisms. Am J Physiol 1998; 275: 1256-64.
86. Maragos CM, Wang JM, Hrabie JA, Oppenheim JJ, Keefer LK. Nitric oxide/nucleophile complexes inhibit the in vitro proliferation of A375 melanoma cells via nitric oxide release. Cancer Res 1993; 53(3): 564-8.
87. Gansauge S, Nussler AK, Berger HG, Gansague F. Nitric oxide-induced apoptosis in human pancreatic carcinoma cell lines is associated with G1- arrest and an increase of the cyclin-dependent kinase inhibitor p21WAF1 / CIP1. Cell Growth Differ 1998; 9: 611-7.
88. Huguenin S, Fleury-Feith J, Kheuang L, Jaurand MC, Bolla M, Riffaud JP, et al. Nitrosulindac (NCX 1102): a new nitric oxide-donating non-steroidal anti-inflammatory drug (NO-NSAID), inhibits proliferation and induces apoptosis in human prostatic epithelial cell lines. Prostate 2004; 61(2): 132-41.
89. Jarry A, Charrier L, Bou-Hanna C, Devilder M-C, Crussaire V, Denis MG, et al. Position in cell cycle controls the sensitivity of colon cancer cells to nitric oxide-dependent programmed cell death. Cancer Res 2004; 64: 4227-34.
90. Stotz W, Li D, Johns RA. Exogenous nitric oxide upregulates p21waf1 / cip1 in pulmonary microvascular smooth muscle cells. J Vasc Res 2004; 41: 211-9.
91. Gu M, Brecher P. Nitric oxide-induced increase in p21Sdi1 / Cip1 / Waf1 expression during the cell cycle in aortic adventitial fibroblasts. Arterioscler Thromb Vasc Biol 2000; 20: 27-34.
92. Gu M, Lynch J, Brecher P. Nitric oxide increases p21Waf1 / Cip1 expression by a cGMP-dependent pathway that includes activation of extracellular signal-regulated kinase and p70S6k. J Biol Chem 2000; 275: 11389-96.
93. Wedgwood S, Black SM. Molecular mechanisms of nitric oxide-induced growth arrest and apoptosis in fetal pulmonary arterial smooth muscle cells. Nitric Oxide 2003; 9: 201-10.
94. Bauer PM, Buga GM, Fukuto JM, Pegg AE, Ignarro LJ. Nitric oxide inhibits ornithine decarboxylase via S-nitrosylation of cystein 360 in the active site of the enzyme. J Biol Chem 2001; 276: 34458-64.
95. Costa RS, Assreuy J. Nitric oxide inhibits irreversibly P815 cell proliferation: involvement of potassium channels. Cell Prolif 2002; 35: 321-32.
96. Ishida A, Sasaguri T, Kosaka C, Nojima H, Ogata J. Induction of the cyclin-dependent kinase inhibitor p21Sdi1 / Cif1 / Waf1 by nitric oxide-generating vasodilator in vascular smooth muscle cells. J Biol Chem 1997; 272: 10050-7.
97. Guo K, Andre's V, Walsh K. Nitric oxideinduced downregulation of Cdk2 activity and cyclin A gene transcription in vascular smooth muscle cells. Circulation 1998; 97: 2066-72.
98. Villalobo A. Nitric oxide and cell proliferation. FEBS J 2006; 273: 2329-44.
99. Lander HM, Ogiste JS, Pearce SFA, Levi R, Novogrodsky A. Nitric oxide-stimulated guanine nucleotide exchange on p21ras. J Biol Chem 1995; 270: 7020.
100. Lander HM, Milbank AJ, Tauras JM, Hempstead HBL, Schwartz GD, Kraemer R. Redox regulation cell signalling. Nature 1996; 381: 380-1.
101. Cha MS, Lee MJ, Je GH, Kwak JY. Endogenous production of nitric oxide by vascular endothelial growth factor down-regulates proliferation of choriocarcinoma cells. Biochem Biophys Res Commun 2001; 282: 1061-6.
102. Du M, Islam MM, Lin L, Ohmura Y, Moriyama Y, Fujimura S. Promotion of proliferation of murine BALB/ C3T3 fibroblasts mediated by nitric oxide at lower concentrations. Biochem Mol Biol Int 1997; 41: 625-31.
103. Hajri A, Metzger E, Vallat F, Coffy S, Flatter E, Evrard S, et al. Role of nitric oxide in pancreatic tumor growth: in vivo and in vitro studies. Br J Cancer 1998; 78: 841-9.
104. Ulibarri JA, Mozdziak PE, Schultz E, Cook C, Best TM. Nitric oxide donors, sodium nitroprusside and S-nitro-N-acetylpencillamine, stimulate myoblast proliferation in vitro. In Vitro Cell Dev Biol Anim 1999; 35: 215-8.
105. Krischel V, Bruch-Gerharz D, Suschek C, Kröncke K-D, Ruzicka T, Kolb-Bachofen V. Biphasicn effect of exogenous nitric oxide on proliferation and differentiation in skin derived keratinocytes but not fibroblasts. J Invest Dermatol 1998; 111: 286-91.
106. Frank S, Kämpfer H, Podda M, Kaufmann R, Pfeilschifter J. Identification of copper / zinc superoxide dismutase as a nitric oxide-regulated gene in human (HaCaT) keratinocytes: implications for keratinocyte proliferation. Biochem J 2000; 346: 719-28.
107. Luczak K, Balcerczyk A, Soszynski M, Bartosz G. Low concentration of oxidant and nitric oxide donors stimulate proliferation of human endothelial cells in vitro. Cell Biol Int 2004; 28: 483-6.
108. Wai PY, Guo L, Gao C, Mi Z, Guo H, Kuo PC. Osteopontin inhibits macrophage nitric oxide synthesis to enhance tumor proliferation. Surgery 2006; 140: 132-40.
109. Tanriover N, Ulu MO, Isler C, Durak H, Oz B, Uzan M, et al. Neuronal nitric oxide synthase expression in glial tumors: correlation with malignancy and tumor proliferation. Neurol Res 2008; 30: 940-4.
110. Fiszman GL, Middonno MC, de la Torre E, Farina M, Español AJ, Sales ME. Activation of muscarinic cholinergic receptors induces MCF-7 cells proliferation and angiogenesis by stimulating nitric oxide synthase activity. Cancer Biol Ther 2007; 6: 1106-13.
111. Lind DS. Arginine and cancer. J Nutr 2004; 134: 2837-41.
112. Lala PK, Orucevic A. Role of nitric oxide in tumor progression: lessons from experimental tumors. Cancer Metastasis Rev 1998; 17: 91-106.
113. Williams EL, Djamgoz MB. Nitric oxide and metastatic cell behaviour. Bioessays 2005; 27: 1228-38.
114. Mocellin S. Nitric oxide: cancer target or anticancer agent? Curr Cancer Drug Targets 2009; 9: 214-36.
115. Tatemichi M, Ogura T, Esumi H. Impact of inducible nitric oxide synthase gene on tumor progression. Eur J Cancer Prev 2009; 18: 1-8.
116. Lechner M, Lirk P, Rieder J. Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin. Semin Cancer Biol 2005; 15: 277-89.
117. Hauptmann S, Siegert A, Berger S, Denkert C, Kobel M, Ott S, et al. Regulation of cell growth and the expression of extracellular matrix proteins in colorectal adenocarcinoma: a fibroblast-tumor cell coculture model to study tumor-host interactions in vitro. Eur J Cell Biol 2003; 82: 1-8.
118. Roth JM, Akalu A, Zelmanovich A, Policarpio D, Ng B, MacDonald S, et al. Recombinant alpha2(IV)NC1 domain inhibits tumor cell-extracellular matrix interactions, induces cellular senescence, and inhibits tumor growth in vivo. Am J Pathol 2005; 166: 901-11.
119. Sangaletti S, Di Carlo E, Gariboldi S, Miotti S, Cappetti B, Parenza M, et al. Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis. Cancer Res 2008; 68: 9050-9.
120. Qiu H, Orr FW, Jensen D, Wang HH, McIntosh AR, Hasinoff BB, et al. Arrest of B16 melanoma cells in the mouse pulmonary microcirculation induces endothelial nitric oxide synthase-dependent nitric oxide release that is cytotoxic to the tumor cells. Am J Pathol 2003; 162: 403-12.
121. Qi K, Qiu H, Rutherford J, Zhao Y, Nance DM, Orr FW. Direct visualization of nitric oxide release by liver cells after the arrest of metastatic tumor cells in the hepatic microvasculature. J Surg Res 2004; 119: 29-35.
122. Wang F, Zhang R, Xia T, Hsu E, Cai Y, Gu Z, et al. Inhibitory effects of nitric oxide on invasion of human cancer cells. Cancer Lett 2007; 257: 274-82.
123. Simeone AM, Colella S, Krahe R, Johnson MM, Mora E, Tari AM. N-(4-Hydroxyphenyl)retinamide and nitric oxide pro-drugs exhibit apoptotic and anti-invasive effects against bone metastatic breast cancer cells. Carcinogenesis 2006; 27: 568-77.
124. Simeone AM, McMurtry V, Nieves-Alicea R, Saavedra JE, Keefer LK, Johnson MM, et al. TIMP-2 mediates the anti-invasive effects of the nitric oxide-releasing prodrug JS-K in breast cancer cells. Breast Cancer Res 2008; 10: R44.
125. Chen JH, Lin HH, Chiang TA, Hsu JD, Ho HH, Lee YC, et al. Gaseous nitrogen oxide promotes human lung cancer cell line A549 migration, invasion, and metastasis via iNOS-mediated MMP-2 production. Toxicol Sci 2008; 106: 364-75.
126. Fukumura D, Kashiwagi S, Jain RK. The role of nitric oxide in tumor progression. Nat Rev Cancer 2006; 6: 521-34.
127. Yasuoka H, Kodama R, Hirokawa M, Takamura Y, Miyauchi A, Sanke T, et al. CXCR4 expression in papillary thyroid carcinoma: induction by nitric oxide and correlation with lymph node metastasis. BMC Cancer 2008; 8: 274.
128. Yasuoka H, Tsujimoto M, Yoshidome K, Nakahara M, Kodama R, Sanke T, et al. Cytoplasmic CXCR4 expression in breast cancer: induction by nitric oxide and correlation with lymph node metastasis and poor prognosis. BMC Cancer 2008; 8: 340.
129. Nakamura Y, Yasuoka H, Tsujimoto M, Yoshidome K, Nakahara M, Nakao K, et al. Nitric oxide in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis. Clin Cancer Res 2006; 12: 1201-7.
130. Nakamura Y, Yasuoka H, Zuo H, Takamura Y, Miyauchi A, Nakamura M, et al. Nitric oxide in papillary thyroid carcinoma: induction of vascular endothelial growth factor D and correlation with lymph node metastasis. J Clin Endocrinol Metab 2006; 91: 1582-5.
131. Guo H, Marroquin CE, Wai PY, Kuo PC. Nitric oxide-dependent osteopontin expression induces metastatic behavior in HepG2 cells. Dig Dis Sci 2005; 50: 1288-98.
132. Ali SM, Olivo M. Nitric oxide mediated photo-induced cell death in human malignant cells. Int J Oncol 2003; 22: 751-6.
133. Hirst DG, Robson T. Nitrosative stress in cancer therapy. Front Biosci 2007; 12: 3406-18.
134. Loibl S, von Minckwitz G, Weber S, Sinn HP, Schini-Kerth VB, Lobysheva I, et al. Expression of endothelial and inducible nitric oxide synthase in benign and malignant lesions of the breast and measurement of nitric oxide using electron paramagnetic resonance spectroscopy. Cancer 2002; 95: 1191-8.
135. Decker NK, Abdelmoneim SS, Yaqoob U, Hendrickson H, Hormes J, Bentley M, et al. Nitric oxide regulates tumor cell cross-talk with stromal cells in the tumor microenvironment of the liver. Am J Pathol 2008; 173: 1002-12.
136. Wei D, Richardson EL, Zhu K, Wang L, Le X, He Y, et al. Direct demonstration of negative regulation of tumor growth and metastasis by host-inducible nitric oxide synthase. Cancer Res 2003; 63: 3855-9.
137. Shi Q, Huang S, Jiang W, Kutach LS, Ananthaswamy HN, Xie K. Direct correlation between nitric oxide synthase II inducibility and metastatic ability of UV-2237 murine fibrosarcoma cells carrying mutant p53. Cancer Res 1999; 59: 2072-5.
138. Wang B, Wei D, Crum VE, Richardson EL, Xiong HH, Luo Y, et al. A novel model system for studying the double-edged roles of nitric oxide production in pancreatic cancer growth and metastasis. Oncogene 2003; 22: 1771-82.
139. Le X, Wei D, Huang S, Lancaster JR, Xie K. Nitric oxide synthase II suppresses the growth and metastasis of human cancer regardless of its up-regulation of protumor factors. Proc Natl Acad Sci USA 2005; 102: 8758-63.
140. Wang HH, McIntosh AR, Hasinoff BB, Rector ES, Ahmed N, Nance DM, et al. B16 melanoma cell arrest in the mouse liver induces nitric oxide release and sinusoidal cytotoxicity: a natural hepatic defense against metastasis. Cancer Res 2000; 60: 5862-9.
141. Pipili-Synetos E, Papageorgiou A, Sakkoula E, Sotiropoulou G, Fotsis T, Karakiulakis G, et al. Inhibition of angiogenesis, tumor growth and metastasis by the NO-releasing vasodilators, isosorbide mononitrate and dinitrate. Br J Pharmacol 1995; 116: 1829-34.
142. Sayed-Ahmad MM, Mohamad MA. Contribution of nitric oxide and epidermal growth factor receptor in anti-metastatic potential of paclitaxel in human liver cancer cell (HebG2). J Egypt Natl Cancer Inst 2005; 17: 35-41.
143. Gatti G, Simsek S, Zurrida S, Kurne A, Giannetti I, Demirer S, et al. Possible role of nitric oxide in the biology of breast carcinoma: review of the available literature. Breast 2004; 13: 1-6.
144. Xie K, Fidler IJ. Therapy of cancer metastasis by activation of the inducible nitric oxide synthase. Cancer Metastasis Rev 1998; 17: 55-75.
145. Fidler IJ, Ellis LM. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell 1994; 79: 185-8.
146. Matevossian E, Novotny A, Knebel C, Brill T, Werner M, Sinicina I, et al. The effect of selective inhibition of inducible nitric oxide synthase on cytochrome P450 after liver transplantation in a rat model. Transpl Proc 2008; 40: 983-5.
147. Singh D, Richards D, Knowles RG, Schwartz S, Woodcock A, Langley S, et al. Selective inducible nitric oxide synthase inhibition has no effect on allergen challenge in asthma. Am J Respir Crit Care Med 2007; 176: 988-93.
148. Edwards PD, Topping D, Kontaridis MI, Moldawer LL, Copeland EM 3rd, Lind DS. Arginine-enhanced enteral nutrition augments the growth of a nitric oxide-producing tumor. JPEN J Parenter Enteral Nutr 1997; 21: 215-9.
149. Jadeski LC, Chakraborty C, Lala PK. Role of nitric oxide in tumor progression with special reference to a murine breast cancer model. Can J Physiol Pharmacol 2002; 80: 125-35.
150. Jurasz P, Sawicki G, Duszyk M, Sawicka J, Miranda C, Mayers I, et al. Matrix metalloproteinase 2 in tumor cell-induced platelet aggregation: regulation by nitric oxide. Cancer Res 2001; 61: 376-82.
151. Adithi M, Nalini V, Kandalam M, Krishnakumar S. Expression of matrix metalloproteinases and their inhibitors in retinoblastoma. J Pediatr Hematol Oncol 2007; 29: 399-405.
152. Arvelo F, Cotte C. Metalloproteinases in tumor progression. Review. Invest Clin 2006; 47: 185-205.
153. Hickery MS, Bayliss MT. Interleukin-1 induced nitric oxide inhibits sulphation of glycosaminoglycan chains in human articular chondrocytes. Biochim Biophys Acta 1998; 1425: 282-90.
154. Game X, Allard J, Escourrou G, Gourdy P, Tack I, Rischmann P, et al. Estradiol increases urethral tone through the local inhibition of neuronal nitric oxide synthase expression. Am J Physiol Regul Integr Comp Physiol 2008; 294: R851-7.
155. Tsukimori K, Komatsu H, Fukushima K, Kaku T, Nakano H, Wake N. Inhibition of nitric oxide synthetase at mid-gestation in rats is associated with increases in arterial pressure, serum tumor necrosis factor-alpha, and placental apoptosis. Am J Hypertens 2008; 21: 477-81.
156. Siegert A, Rosenberg C, Schmitt WD, Denkert C, Hauptmann S. Nitric oxide of human colorectal adenocarcinoma cell lines promotes tumor cell invasion. Br J Cancer 2002; 86: 1310-5.
157. Jadeski LC, Hum KO, Chakraborty C, Lala PK. Nitric oxide promotes murine mammary tumor growth and metastasis by stimulating tumor cell migration, invasiveness and angiogenesis. Int J Cancer 2000; 86: 30-9.
158. Hengartner MO. The biochemistry of apoptosis, Nature 2000; 407: 770-6.
159. Brune B. Nitric oxide: NO apoptosis or turning it ON? Cell Death Differ 2003; 10: 864-9.
160. Brune B. The intimate relation between nitric oxide and superoxide in apoptosis and cell survival. Antioxid Redox Signal 2005; 7: 497-507.
161. Friebe A, Koesling D. Regulation of nitric oxidesensitive guanylyl cyclase. Circ Res 2003; 93: 96-105.
162. Secchiero P, Gonelli A, Celeghini C, Mirandola P, Guidotti L, Visani G, et al. Activation of the nitric oxide synthase pathway represents a key component of tumor necrosis factor-related apoptosis-inducing ligandmediated cytotoxicity on hematologic malignancies. Blood 2001; 98: 2220-8.
163. Garbán HJ, Bonavida B. Nitric oxide sensitizes ovarian tumor cells to Fasinduced apoptosis. Gynecol Oncol 1999; 73: 257-64.
164. Zou H, Li Y, Liu X, Wang X. An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 1999; 274: 11549-56.
165. Sedlak TW, Snyder SH. Messenger molecules and cell death: therapeutic implications. JAMA 2006; 295: 81-9.
166. Marshall HE, Stamler JS. Inhibition of NF-kappa B by S-nitrosylation. Biochemistry 2001; 40: 1688-93.
167. Hong YH, Peng HB, La Fata V, Liao JK. Hydrogen peroxide-mediated transcriptional induction of macrophage colony-stimulating factor by TGFbeta1. J Immunol 1997; 159: 2418-23.
168. Schreck R, Albermann K, Baeuerle PA. Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Radic Res Commun 1992; 17: 221-37.
169. Wang X, Zalcenstein A, Oren M. Nitric oxide promotes p53 nuclear retention and sensitizes neuroblastoma cells to apoptosis by ionizing radiation. Cell Death Differ 2003; 10: 468-76.
170. Oren M. Decision making by p53: life, death and cancer. Cell Death Differ 2003; 10: 431-42.
171. Ishida A, Sasaguri T, Miwa Y, Kosaka C, Taba Y, Abumiya T. Tumor suppressor p53 but not cGMP mediates NO-induced expression of p21(Waf1/ Cip1/Sdi1) in vascular smooth muscle cells. Mol Pharmacol 1999; 56: 938-46.
172. Tian B, Liu J, Bitterman PB, Bache RJ. Mechanisms of cytokine induced NOmediated cardiac fibroblast apoptosis. Am J Physiol Heart Circ Physiol 2002; 283: H1958-67.
173. Lala PK, Chakraborty C. Role of nitric oxide in carcinogenesis and tumor progression. Lancet Oncol 2001; 2: 149-56.
174. Wink DA. The role of nitric oxide chemistry in cancer treatment. Biochem Mosc 1998; 63: 802-9.
175. Ekmekcioglu S, Tang CH, Grimm EA. NO news is not necessarily good news in cancer. Curr Cancer Drug Targets 2005; 5: 103-15.
176. Mannick JB, Schonhoff CM. NO means no and yes: regulation of cell signaling by protein nitrosylation. Free Radic Res 2004; 38: 1-7.
177. Chung HT, Pae HO, Choi BM, Billiar TR, Kim YM. Nitric oxide as a bioregulator of apoptosis. Biochem Biophys Res Commun 2001; 282: 1075-9.
178. Blaise GA, Gauvin D, Gangal M, Authier S. Nitric oxide, cell signaling and cell death.Toxicology 2005; 208: 177-92.
179. Dash PR, Cartwright JE, Baker PN, Johnstone AP, Whitley GS. Nitric oxide protects human extravillous trophoblast cells from apoptosis by a cyclic GMP-dependent mechanism and independently of caspase 3 nitrosylation. Exp Cell Res 2003; 287: 314-24.
180. Olson SY, Garbán HJ. Regulation of apoptosis-related genes by nitric oxide in cancer. Nitric Oxide 2008; 19: 170-6.
181. Jones MK, Tsugawa K, Tarnawski AS, Baatar D. Dual actions of nitric oxide on angiogenesis: possible roles of PKC, ERK, and AP-1. Biochem Biophys Res Commun 2004; 318: 520-8.
182. Ambs S. p53 and vascular endothelial growth factor regulate tumor growth of NOS2-expressing human carcinoma cells. Nat Med 1998; 4: 1371-6.
183. Zhang J, Dawson VL, Dawson TM, Snyder SH. Nitric oxide activation of poly (ADP-ribose) synthetase in neurotoxicity. Science 1994; 263: 687-9.
184. Hussain SP. Nitric oxide, a mediator of inflammation, suppresses tumorigenesis. Cancer Res 2004; 64: 6849-53.
185. Thomas DD, Espey MG, Ridnour LA, Hofseth LJ, Mancardi D, Harris CC, et al. Hypoxic inducible factor 1alpha, extracellular signal-regulated kinase, and p53 are regulated by distinct threshold concentrations of nitric oxide. Proc Natl Acad Sci USA 2004; 101: 8894-9.
186. Pervin S, Singh R, Freije WA, Chaudhuri G. 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 2003; 63: 8853-60.
187. Hussain SP, Harris CC. p53 biological network: at the crossroads of the cellular-stress response pathway and molecular carcinogenesis. J Nippon Med Sch 2006; 73: 54-64.
188. Prueitt RL, Boersma BJ, Howe TM, Goodman JE, Thomas DD, Ying L, et al. Inflammation and IGF-I activate the Akt pathway in breast cancer. Int J Cancer 2007; 120: 796-805.
189. Stechmiller JK, Childress B, Porter T. Arginine immunonutrition in critically ill patients: a clinical dilemma. Am J Crit Care 2004; 13: 17-23.
190. Ogilvie GK, Fettman MJ, Mallinckrodt CH, Walton JA, Hansen RA, Davenport DJ, et al. Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma: A double-blind, randomised placebo-controlled study. Cancer 2000; 88: 1916-28.
191. Hester JE, Fee WE. Effect of arginine on growth of squamous cell carcinoma in the CH3/KM mouse. Arch Otolaryngol Head Neck Surg 1995; 121: 193-6.
192. Ma Q, Williamson KE, O'rourke D, Rowlands BJ. The effects of L-arginine on crypt cell hyperproliferation in colorectal cancer. J Surg Res 1999; 81: 181-8
193. Bani D, Masini E, Bello MG, Bigazzi M, Sacchi TB. Relaxin activates the L-arginine-nitric oxide pathway in human breast cancer cells. Cancer Res 1995; 55: 5272-5.
194. Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 1992; 12: 5447-54.
195. Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxiainducible factor 1. J Biol Chem 1994; 269: 23757-63.
196. Comerford KM, Wallace TJ, Karhausen J, Louis NA, Montalto MC, Colgan SP. Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res 2002; 15: 3387-94.
197. Semenza GL. Evaluation of HIF-1 inhibitors as anticancer agents. Drug Discov Today 2007; 12: 853-9.
198. Moeller BJ, Dewhirst MW. HIF-1 and tumor radiosensitivity. Br J Cancer 2006; 95: 1-5.
199. Yeo EJ, Chun YS, Cho YS, Kim J, Lee JC, Kim MS, et al. YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1. J Natl Cancer Inst 2003; 95: 516-25.
200. Welsh S, Williams R, Kirkpatrick L, Paine-Murrieta G, Powis G. Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1alpha. Mol Cancer Ther 2004; 3: 233-44.
201. Hagen TC, Taylor T, Lam F, Moncada S. Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha. Science 2003; 302: 1975-8.
202. Yasuda H, Nakayama K, Watanabe M, Suzuki S, Fuji H, Okinaga S, et al. Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma. Clin Cancer Res 2006; 12: 6748-57.
203. Perrotta C, Falcone S, Capobianco A, Camporeale A, Sciorati C, De Palma C, et al. Nitric oxide confers therapeutic activity to dendritic cells in a mouse model of melanoma. Cancer Res 2004; 64: 3767-71.
204. Yasuda H, Nakayama K, Watanabe M, Kaneta T, Asada M, Sasaki T, et al. Nitroglycerin may increase response to anticancer drugs in non-small cell lung cancer via reduction of HIF-1α pathway. Nitric Oxide 2007; 17: S15, A24.
205. Bullock AN, Fersht AR. Rescuing the function of mutant p53. Nat Rev Cancer 2001; 1: 68-76.
206. Lowe SW, Ruley HE, Jacks T, Houseman DE. P53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 1993; 74: 957-67.
207. Yasuda H, Yamaya M, Nakayama K, Sasaki T, Ebihara S, Kanda A, et al. Randomized phase II trial comparing nitroglycerin plus vinorelbine and cisplatin with vinorelbine and cisplatin alone in previously untreated stage IIIB/IV non-small cell lung cancer. J Clin Oncol 2006; 24: 688-94.
208. Riganti CE, Miraglia D, Viarisio C, Costamagna G, Pescarmona D, Ghigo A, et al. Nitric oxide reverts the resistance to doxorubicin in human colon cancer cells by inhibiting the drug efflux. Cancer Res 2005; 65: 516-25.
209. Wink DA, Cook JA, Christodoulou D, Krishna MC, Pacelli R, Kim S, et al. Nitric oxide and some nitric oxide donor compounds enhance the cytotoxicity of cisplatin. Nitric Oxide 1997; 1: 88-94.
210. Azizzadeh B, Yip HT, Blackwell KE, Horvath S, Calcaterra TC, Buga GM, et al. Nitric oxide improves cisplatin cytotoxicity in head and neck squamous cell carcinoma. Laryngoscope 2001; 111: 1896-900.
211. Frederiksen LJ, Sullivan R, Maxwell LR, Macdonald-Goodfellow SK, Adams MA, Bennett BM, et al. Chemosensitization of cancer in vitro and in vivo by nitric oxide signaling. Clin Cancer Res 2007; 13: 2199-206.
212. Laval F, Wink DA. Inhibition by nitric oxide of the repair protein, O6-methylguanine-DNA-methyltransferase. Carcinogenesis 1994; 15: 443-7.
213. Cook JA, Krishna MC, Pacelli R, DeGraff W, Liebmann J, Mitchell JB, et al. Nitric oxide enhancement of melphalan-induced cytotoxicity. Br J Cancer 1997; 76: 325-34.
214. Lee JM, Bernstein A. p53 mutations increase resistance to ionizing radiation. Proc Natl Acad Sci USA 1993; 90: 5742-6.
215. Morales A, Miranda M, Sánchez-Reyes A, Biete A, Fernández-Checa JC. Oxidative damage of mitochondrial and nuclear DNA induced by ionizing radiation in human hepatoblastoma cells. J Radiat Oncol Biol Phys 1998; 42: 191-203.
216. Howard-Flanders P. Effect of nitric oxide on the radiosensitivity of bacteria. Nature 1957; 180: 1191-2.
217. Mitchell JB, Wink DA, DeGraff W, Gamson J, Keefer LK, Krishna MC. Hypoxic mammalian cell radiosensitization by nitric oxide. Cancer Res 1993; 53: 5845-8.
218. Wood PJ, Stratford IJ, Adams GE, Szabo C, Thiemermann C, Vane JR. Modification of energy metabolism and radiation response of a murine tumor by changes in nitric oxide availability. Biochem Biophys Res Commun 1993; 192: 505-10.
219. Schneiderhan N, Budde A, Zhang Y, Brune B. Nitric oxide induces phosphorylation of p53 and impairs nuclear export. Oncogene 2003; 22: 2857-68.
220. Unger T, Sionov RV, Moallem E, Yee CL, Howley PM, Oren M, et al. Mutations in serines 15 and 20 of human p53 impair its apoptotic activity. Oncogene 1999; 18: 3205-12.
221. Wang Z, Cook T, Alber S, Liu K, Kovesdi I, Watkins SK, et al. 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 2004; 64: 1386-95.
222. Cook T, Wang Z, Alber S, Liu K, Watkins SC, Vodovotz Y, et al. Nitric oxide and ionizing radiation synergistically promote apoptosis and growth inhibition of cancer by activating p53. Cancer Res 2004; 64: 8015-21.
223. Ng CP, Bonavida B. A new challenge for successful immunotherapy by tumors that are resistant to apoptosis: two complementary signals to overcome cross-resistance. Adv Cancer Res 2002; 85: 145-74.
224. Poehlein CH, Hu HM, Yamada J, Assmann I, Alvord WG, Urba WJ, et al. TNF plays an essential role in tumor regression after adoptive transfer of perforin/IFN-gamma double knockout effector T cells. J Immunol 2003; 15: 2004-13.
225. Mori S, Jewett A, Cavalcanti M, Murakami-Mori K, Nakamura S, Bonovida B. Differential regulation of human NK cell-associated gene expression following activation by IL-2, IFN-alpha and PMA/ionomycin. Int J Oncol 1998; 12: 1165-70.
226. Geller DA, Nussler AK, Di Silvio M, Lowenstein CJ, Shapiro RA, Wang SC, et al. Cytokines, endotoxin, and glucocorticoids regulate the expression of inducible nitric oxide synthase in hepatocytes. Proc Natl Acad Sci USA 1993; 90: 522-6.
227. Bonavida B, Baritaki S, Huerta-Yepez S, Vega MI, Chatterjee D, Yeung K. Novel therapeutic applications of nitric oxide donors in cancer: Roles in chemo-and immunosensitization to apoptosis and inhibition of metastases. Nitric Oxide 2008; 19: 152-7.
228. Garbán HJ, Bonavida B. 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 2001; 167: 75-8.
229. Hongo F, Garbán H, Huerta-Yapez S, Vega M, Jazirehi AR, Mizutani Y, et al. Inhibition of the transcription factor Yin Yang 1 activity by S-nitrosation. Biochem Biophys Res Commun 2005; 336: 692-701.
230. Huerta-Yapez S, Vega M, Jazirehi A, Garbán H, Hongo F, Cheng G, et al. Nitric oxide sensitizes prostate carcinoma cell lines to TRAIL-mediated apoptosis via inactivation of NF-jB and Inhibition of Bcl-xL expression. Oncogene 2004; 23: 4993-5003.
231. Matthews NE, Adams MA, Maxwell LR, Gofton TE, Graham CH. Nitric oxide-mediated regulation of chemosensitivity in cancer cells. J Natl Cancer Inst 2001; 93: 1879-85.
232. Graham CH, Hu N, Sheikhi K, Chung E, Pross H, Siemens DR. Hypoxia increases the shedding of MHC class I chain-related molecula (MIC) from the surface of tumor cells: Involvement of nitric oxide signaling. Nitric Oxide 2007; 17: S22, C11.
233. Xie K, Huang S, Dong Z, Juang SH, Gutman M, Xie QW, et al. Transfection with the inducible nitric oxide synthase gene suppresses tumorigenicity and abrogates metastasis by K-1735 murine melanoma cells. J Exp Med 1995; 181: 1333-43.
234. Xie K, Huang S, Dong Z, Juang SH, Wang Y, Fidler IJ. Destruction of bystander cells by tumor cells transfected with inducible nitric oxide (NO) synthase gene. J Natl Cancer Inst 1997; 89: 421-7.
235. Xie K, Bielenberg D, Huang S, Xu L, Salas T, Juang SH, et al. Abrogation of tumorigenicity and metastasis of murine and human tumor cells by transfection with the murine IFN-beta gene: Possible role of nitric oxide. Clin Cancer Res 1997; 3: 2283-94.
236. Xie K, Wang Y, Huang S, Xu L, Bielenberg D, Salas T, et al. Nitric oxide-mediated apoptosis of K-1735 melanoma cells is associated with downregulation of Bcl-2. Oncogene 1997; 15: 771-9.
237. Juang SH, Xie K, Xu L, Shi Q, Wang Y, Yoneda J, et al. Suppression of tumorigenicity and metastasis of human renal carcinoma cells by infection with retroviral vectors harboring the murine inducible nitric oxide synthase gene. Hum Gene Ther 1998; 9: 845-54.
238. Harada K, Supriatno, Kawaguchi S, Tomitaro O, Yoshida H, Sato M. Overexpression of iNOS gene suppresses the tumorigenicity and metastasis of oral cancer cells. In Vivo 2004; 18: 449-55.
239. Khare PD, Shao-Xi L, Kuroki M, Hirose Y, Arakawa F, Nakamura K, Tomita Y, et al. Specifically targeted killing of carcinoembryonic antigen (CEA)-expressing cells by a retroviral vector displaying single-chain variable fragmented antibody to CEA and carrying the gene for inducible nitric oxide synthase. Cancer Res 2001; 61: 370-5.
240. Jordan BF, Sonveaux P, Feron O, Gregoire V, Beghein N, Dessy C, et al. Nitric oxide as a radiosensitizer: evidence for an intrinsic role in addition to its effect on oxygen delivery and consumption. Int J Cancer 2004; 109: 768-73.
241. Adams C, McCarthy HO, Coulter JA, Worthington J, Murphy C, Robson T, et al. Nitric oxide synthase gene therapy enhances the toxicity of cisplatin in cancer cells. J Gene Med 2009; 11: 160-8.
242. Soler MN, Bobe P, Benihoud K, Lemaire G, Roos BA, Lausson S. Gene therapy of rat medullary thyroid cancer by naked nitric oxide synthase II DNA injection. J Gene Med 2000; 2: 344-52.
243. Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, et al. Chemopreventive and therapeutic effects of curcumin. Cancer Lett 2005; 223: 181-90.
244. Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, et al. Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/ progression stages of colon cancer. Cancer Res 1999; 59: 597-601.
245. Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, et al. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: Down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 2001; 481: 243-68.
246. Wu J, Akaike T, Maeda H. Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger. Cancer Res 1998; 58: 159-65.
247. Zhang HJ, Zhao W, Venkataraman S, Robbins ME, Buettner GR, Kregel KC, et al. Activation of matrixmetalloproteinase-2 by overexpression ofmanganese superoxide dismutase in human breast cancer MCF-7 cells involves reactive oxygen species. J Biol Chem 2002; 277: 20919-26.
248. Jadeski LC, Lala PK. Nitric oxide synthase inhibition by N(G)-nitro-L-arginine methyl ester inhibits tumor-induced angiogenesis in mammary tumors. Am J Pathol 1999; 155: 1381-90.
249. Uneda S, Hata H, Matsuno F, Nagasaki A, Harada N, Mitsuya Y, et al. A nitric oxide synthase inhibitor, N(G)-nitro-l-arginine-methylester, exerts potent antiangiogenic effects on plasma-cytoma in a newly established multiple myeloma severe combined immunodeficient mouse model. Br J Haematol 2003; 120: 396-404.
250. Thomsen LL. Selective inhibition of inducible nitric oxide synthase inhibits tumor growth in vivo: studies with 1400W, a novel inhibitor. Cancer Res 1997; 57: 3300-4.
251. Chen T, Nines RG, Peschke SM, Kresty LA, Stoner GD. Chemopreventive effects of a selective nitric oxide synthase inhibitor on carcinogen-induced rat esophageal tumorigenesis. Cancer Res 2004; 64: 3714-7.
252. Rao CV, Kawamori T, Hamid R, Reddy BS. Chemoprevention of colonic aberrant crypt foci by an inducible nitric oxide synthase-selective inhibitor. Carcinogenesis 1999; 20: 641-4.
253. Rao CV, Indranie C, Simi B, Manning PT, Connor JR, Reddy BS. 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 2002; 62: 165-70.
254. Ahn B, Ohshima H. Suppression of intestinal polyposis in Apc (Min/p) mice by inhibiting nitric oxide production. Cancer Res 2001; 61: 8357-60.
255. Gratton JP. Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice. Cancer Cell 2003; 4: 31-9.
256. Brouet A. Antitumor effects of in vivo caveolin gene delivery are associated with the inhibition of the proangiogenic and vasodilatory effects of nitric oxide. FASEB J 2005; 19: 602-4.
257. De Santo C, Serafini P, Marigo I. Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proc Natl Acad Sci USA 2005; 102: 4185-90.
258. Ma Q, Wang Y, Gao X, Ma Z, Song Z. L-arginine reduces cell proliferation and ornithine decarboxylase activity in patients with colorectal adenoma and adenocarcinoma. Clin Cancer Res 2007; 13: 7407-12.
259. Burnstock G. Purinergic receptors and pain. Curr Pharm Des 2009; 15(15): 1717-35.
260. Feun L, You M, Wu CJ, Kuo MT, Wangpaichitr M, Spector S, Savaraj N. Arginine deprivation as a targeted therapy for cancer. Curr Pharm Des 2008; 14(11): 1049-57.
261. Yamagishi S, Ueda S, Nakamura K, Matsui T, Okuda S. Role of asymmetric dimethylarginine (ADMA) in diabetic vascular complications. Curr Pharm Des 2008; 14(25): 2613-8.