The effects of Nrf2 on tumor angiogenesis: A review of the possible mechanisms of action

Critical Reviews in Eukaryotic Gene Expression

Volumn 22, Issue 2, 2012, Pages 149-160

  Zhou, Suna ^a,b   Ye, Wenguang ^a   Zhang, Mingxin ^a   Liang, Jun ^a  

^a FOURTH MILITARY MEDICAL UNIVERSITY   (China)

^b XI'AN JIAOTONG UNIVERSITY   (China)

Author keywords

Mechanism; Nrf2; Tumor angiogenesis

Indexed keywords

ANGIOGENESIS MODULATOR; BETA CATENIN; HEME OXYGENASE 1; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 8; KELCH LIKE ECH ASSOCIATED PROTEIN 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROTEIN P53; REACTIVE OXYGEN METABOLITE; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR NRF2; VASCULOTROPIN;

ANTIANGIOGENIC GENE THERAPY; ANTIOXIDANT ACTIVITY; APOPTOSIS; CANCER CELL; CANCER INVASION; CELL HYPOXIA; CELL PROLIFERATION; ENDOMETRIUM CARCINOMA; ENDOTHELIUM; GALLBLADDER CANCER; GENE OVEREXPRESSION; GENE SILENCING; HUMAN; LIVER CELL CARCINOMA; LUNG CANCER; METASTASIS; MOLECULAR INTERACTION; OVARY CANCER; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; REVIEW; THYROID CANCER; TUMOR GROWTH; TUMOR MICROENVIRONMENT; TUMOR VASCULARIZATION;

ANIMALS; ANTIOXIDANTS; ENDOTHELIAL CELLS; GENE EXPRESSION REGULATION, NEOPLASTIC; HEME OXYGENASE-1; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; INTERLEUKIN-9; NEOVASCULARIZATION, PATHOLOGIC; NF-E2-RELATED FACTOR 2; OXIDATIVE STRESS; PROTEIN INTERACTION MAPPING; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84865626729     PISSN: 10454403     EISSN: None     Source Type: Journal    
DOI: 10.1615/CritRevEukarGeneExpr.v22.i2.60     Document Type: Review

References (124)

1. Folkman J, Shing Y. Angiogenesis. J Biol Chem. 1992;267:10931-10934.
2. Hillen F, Griffioen AW. Tumour vascularization: sprouting angiogenesis and beyond. Cancer Metastasis Rev. 2007;26:489-502.
3. di Tomaso E, Capen D, Haskell A, Hart J, Logie JJ, Jain RK, McDonald DM, Jones R, Munn LL. Mosaic tumor vessels: cellular basis and ultrastructure of focal regions lacking endothelial cell markers. Cancer Res. 2005;65:5740-5749.
4. McDonald DM, Choyke PL. Imaging of angiogenesis: from microscope to clinic. Nat Med. 2003;9:713-725.
5. Dvorak HF NJ, Feng D, Dvorak AM. Tumor architecture and targeted delivery. In: Abrams PG FA, editor. Radio-immunotherapy of Cancer. New York: Marcel Dekker; 2000. p. 107-135.
6. Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, Xu L, Hicklin DJ, Fukumura D, di Tomaso E, Munn LL, Jain RK. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell. 2004;6:553-563.
7. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335-2342.
8. Hashizume H, Falcon BL, Kuroda T, Baluk P, Coxon A, Yu D, Bready JV, Oliner JD, McDonald DM. Complementary actions of inhibitors of angiopoietin-2 and VEGF on tumor angiogenesis and growth. Cancer Res. 2010;70:2213-2223.
9. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542-2550.
10. Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Ginsberg MS, Kim ST, Baum CM, DePrimo SE, Li JZ, Bello CL, Theuer CP, George DJ, Rini BI. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24:16-24.
11. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125-134.
12. Li Y, Huang JW, Lu LG, Shao PJ, Hu BS, Huang GM, Wei ZG, Zhang L. Clinical analysis of the treatment:transcatheter arterial chemoembolization combined with sorafenib in advanced hepatocellular carcinoma. Zhonghua Yi Xue Za Zhi. 2010;90:2187-2192.
13. Pignochino Y, Grignani G, Cavalloni G, Motta M, Tapparo M, Bruno S, Bottos A, Gammaitoni L, Migliardi G, Camussi G, Alberghini M, Torchio B, Ferrari S, Bussolino F, Fagioli F, Picci P, Aglietta M. Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways. Mol Cancer. 2009;8:118.
14. Zhang D, Li B, Shi J, Zhao L, Zhang X, Wang C, Hou S, Qian W, Kou G, Wang H, Guo Y. Suppression of tumor growth and metastasis by simultaneously blocking vascular endothelial growth factor (VEGF)-A and VEGF-C with a receptor-immunoglobulin fusion protein. Cancer Res. 2010;70:2495-2503.
15. Kim TH, Hur EG, Kang SJ, Kim JA, Thapa D, Lee YM, Ku SK, Jung Y, Kwak MK. NRF2 blockade suppresses colon tumor angiogenesis by inhibiting hypoxia-induced activation of HIF-1alpha. Cancer Res. 2011;71:2260-2275.
16. Was H, Dulak J, Jozkowicz A. Heme oxygenase-1 in tumor biology and therapy. Curr Drug Targets. 2010;11:1551-1570.
17. Motohashi H, O'Connor T, Katsuoka F, Engel JD, Yamamoto M. Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors. Gene. 2002;294:1-12.
18. Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 1999;13:76-86.
19. Motohashi H, Yamamoto M. Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med. 2004;10:549-557.
20. McMahon M, Thomas N, Itoh K, Yamamoto M, Hayes JD. Redox-regulated turnover of Nrf2 Is determined by at least two separate protein domains, the redox-sensitive Neh2 degron and the redox-insensitive Neh6 degron. J Biol Chem. 2004;279:31556-31567.
21. Nioi P, Nguyen T, Sherratt PJ, Pickett CB. The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation. Mol Cell Biol. 2005;25:10895-10906.
22. Katoh Y, Itoh K, Yoshida E, Miyagishi M, Fukamizu A, Yamamoto M. Two domains of Nrf2 cooperatively bind CBP, a CREB binding protein, and synergistically activate transcription. Genes Cells. 2001;6:857-868.
23. Chen XL, Kunsch C. Induction of cytoprotective genes through Nrf2/antioxidant response element pathway: a new therapeutic approach for the treatment of inflammatory diseases. Curr Pharm Des. 2004;10:879-891.
24. Lee JS, Surh YJ. Nrf2 as a novel molecular target for chemoprevention. Cancer Lett. 2005;224:171-184.
25. Long DJ 2nd, Waikel RL, Wang XJ, Perlaky L, Roop DR, Jaiswal AK. NAD(P)H:quinone oxidoreductase 1 deficiency increases susceptibility to benzo(a)pyrene-induced mouse skin carcinogenesis. Cancer Res. 2000;60:5913-5915.
26. Villeneuve NF, Lau A, Zhang DD. Regulation of the Nrf2-Keap1 antioxidant response by the ubiquitin proteasome system: an insight into cullin-ring ubiquitin ligases. Antioxid Redox Signal. 2010;13:1699-1712.
27. Lo SC, Li X, Henzl MT, Beamer LJ, Hannink M. Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling. EMBO J. 2006;25:3605-3617.
28. Cho HY, Reddy SP, Debiase A, Yamamoto M, Kleeberger SR. Gene expression profiling of NRF2-mediated protection against oxidative injury. Free Radic Biol Med. 2005;38:325-343.
29. Kwak MK, Wakabayashi N, Itoh K, Motohashi H, Yamamoto M, Kensler TW. Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival. J Biol Chem. 2003;278:8135-8145.
30. Vargas MR, Johnson JA. The Nrf2-ARE cytoprotective pathway in astrocytes. Expert Rev Mol Med. 2009;11:e17.
31. Surh YJ, Kundu JK, Na HK. Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med. 2008;74:1526-1539.
32. Zhang DD. Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab Rev. 2006;38:769-789.
33. Cho HY, Kleeberger SR. Nrf2 protects against airway disorders. Toxicol Appl Pharmacol. 2010;244:43-56.
34. Solis LM, Behrens C, Dong W, Suraokar M, Ozburn NC, Moran CA, Corvalan AH, Biswal S, Swisher SG, Bekele BN. Nrf2 and Keap1 Abnormalities in Non-Small Cell Lung Carcinoma and Association with Clinicopathologic Features. Clin Cancer Res. 2010;16:3743-3753.
35. Chen N, Yi X, Abushahin N, Pang S, Zhang D, Kong B, Zheng W. Nrf2 expression in endometrial serous carcinomas and its precancers. Int J Clin Exp Pathol. 2011;4:85-96.
36. Ma R, Zhang M, Wang J, Cai H, Yeer M, Duan X. Expression and distribution of Nrf2 in several hepatocellular carcinoma cell lines. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2011;27:608-610.
37. Konstantinopoulos PA, Spentzos D, Fountzilas E, Francoeur N, Sanisetty S, Grammatikos AP, Hecht JL, Cannistra SA. Keap1 mutations and Nrf2 pathway activation in epithelial ovarian cancer. Cancer Res. 2011;71:5081-5089.
38. Lister A, Nedjadi T, Kitteringham NR, Campbell F, Costello E, Lloyd B, Copple IM, Williams S, Owen A, Neoptolemos JP. Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy. Mol Cancer. 2011;10:37.
39. Du ZX, Yan Y, Zhang HY, Liu BQ, Gao YY, Niu XF, Meng X, Wang HQ. Proteasome inhibition induces a p38 MAPK pathway-dependent antiapoptotic program via Nrf2 in thyroid cancer cells. J Clin Endocrinol Metab. 2011;96:E763-E771.
40. Wang J, Zhang M, Zhang L, Cai H, Zhou S, Zhang J, Wang Y. Correlation of Nrf2, HO-1, and MRP3 in gall-bladder cancer and their relationships to clinicopathologic features and survival. J Surg Res. 2010;164:e99-e105.
41. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407:249-257.
42. Afonyushkin T, Oskolkova OV, Philippova M, Resink TJ, Erne P, Binder BR, Bochkov VN. Oxidized phospholipids regulate expression of ATF4 and VEGF in endothelial cells via NRF2-dependent mechanism: novel point of convergence between electrophilic and unfolded protein stress pathways. Arterioscler Thromb Vasc Biol. 2010;30:1007-1013.
43. Jyrkkanen HK, Kansanen E, Inkala M, Kivela AM, Hurttila H, Heinonen SE, Goldsteins G, Jauhiainen S, Tiainen S, Makkonen H, Oskolkova O, Afonyushkin T, Koistinaho J, Yamamoto M, Bochkov VN, Yla-Herttuala S, Levonen AL. Nrf2 regulates antioxidant gene expression evoked by oxidized phospholipids in endothelial cells and murine arteries in vivo. Circ Res. 2008;103:e1-e9.
44. Ungvari Z, Bagi Z, Feher A, Recchia FA, Sonntag WE, Pearson K, de Cabo R, Csiszar A. Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Physiol Heart Circ Physiol. 2010;299:H18-H24.
45. Ungvari Z, Bailey-Downs L, Gautam T, Jimenez R, Losonczy G, Zhang C, Ballabh P, Recchia FA, Wilkerson DC, Sonntag WE, Pearson K, de Cabo R, Csiszar A. Adaptive induction of NF-E2-related factor-2-driven antioxidant genes in endothelial cells in response to hyperglycemia. Am J Physiol Heart Circ Physiol. 2011;300:H1133-H1140.
46. Bailey-Downs LC, Mitschelen M, Sosnowska D, Toth P, Pinto JT, Ballabh P, Valcarcel-Ares MN, Farley J, Koller A, Henthorn JC, Bass C, Sonntag WE, Ungvari Z, Csiszar A. Liver-specific knockdown of IGF-1 decreases vascular oxidative stress resistance by impairing the Nrf2-dependent antioxidant response: a novel model of vascular aging. J Gerontol A Biol Sci Med Sci. 2012;67:313-329.
47. Valcarcel-Ares MN, Gautam T, Warrington JP, Bailey-Downs L, Sosnowska D, de Cabo R, Losonczy G, Sonntag WE, Ungvari Z, Csiszar A. Disruption of Nrf2 signaling impairs angiogenic capacity of endothelial cells: implications for microvascular aging. J Gerontol A Biol Sci Med Sci. 2012 Jan 4. [Epub ahead of print]
48. North S, Moenner M, Bikfalvi A. Recent developments in the regulation of the angiogenic switch by cellular stress factors in tumors. Cancer Lett. 2005;218:1-14.
49. Durackova Z. Some current insights into oxidative stress. Physiol Res. 2010;59:459-469.
50. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49:1603-1616.
51. Soehnlein O, Zernecke A, Eriksson EE, Rothfuchs AG, Pham CT, Herwald H, Bidzhekov K, Rottenberg ME, Weber C, Lindbom L. Neutrophil secretion products pave the way for inflammatory monocytes. Blood. 2008;112:1461-1471.
52. Uno K, Prow TW, Bhutto IA, Yerrapureddy A, McLeod DS, Yamamoto M, Reddy SP, Lutty GA. Role of Nrf2 in retinal vascular development and the vaso-obliterative phase of oxygen-induced retinopathy. Exp Eye Res. 2010;90:493-500.
53. Guzy RD, Hoyos B, Robin E, Chen H, Liu L, Mansfield KD, Simon MC, Hammerling U, Schumacker PT. Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab. 2005;1:401-408.
54. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307:58-62.
55. Pries AR, Cornelissen AJ, Sloot AA, Hinkeldey M, Dreher MR, Hopfner M, Dewhirst MW, Secomb TW. Structural adaptation and heterogeneity of normal and tumor microvascular networks. PLoS Comput Biol. 2009;5:e1000394.
56. Dewhirst MW, Cao Y, Moeller B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer. 2008;8:425-437.
57. Semenza GL. Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit Rev Biochem Mol Biol. 2000;35:71-103.
58. Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest. 2010;120:694-705.
59. Sacca P, Meiss R, Casas G, Mazza O, Calvo JC, Navone N, Vazquez E. Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer. Br J Cancer. 2007;97:1683-1689.
60. Sass G, Leukel P, Schmitz V, Raskopf E, Ocker M, Neureiter D, Meissnitzer M, Tasika E, Tannapfel A, Tiegs G. Inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice. Int J Cancer. 2008;123:1269-1277.
61. Alaoui-Jamali MA, Bismar TA, Gupta A, Szarek WA, Su J, Song W, Xu Y, Xu B, Liu G, Vlahakis JZ, Roman G, Jiao J, Schipper HM. A novel experimental heme oxygenase-1-targeted therapy for hormone-refractory prostate cancer. Cancer Res. 2009;69:8017-8024.
62. Lee J, Lee SK, Lee BU, Lee HJ, Cho NP, Yoon JH, Choi HR, Kim EC. Upregulation of heme oxygenase-1 in oral epithelial dysplasias. Int J Oral Maxillofac Surg. 2008;37:287-292.
63. Berberat PO, Dambrauskas Z, Gulbinas A, Giese T, Giese N, Kunzli B, Autschbach F, Meuer S, Buchler MW, Friess H. Inhibition of heme oxygenase-1 in creases responsiveness of pancreatic cancer cells to anticancer treatment. Clin Cancer Res. 2005;11:3790-3798.
64. Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006;86:583-650.
65. Rushworth SA, MacEwan DJ. HO-1 underlies resistance of AML cells to TNF-induced apoptosis. Blood. 2008;111:3793-3801.
66. Li CQ, Kim MY, Godoy LC, Thiantanawat A, Trudel LJ, Wogan GN. Nitric oxide activation of Keap1/Nrf2 signaling in human colon carcinoma cells. Proc Natl Acad Sci U S A. 2009;106:14547-14551.
67. Li MH, Jang JH, Na HK, Cha YN, Surh YJ. Carbon monoxide produced by heme oxygenase-1 in response to nitrosative stress induces expression of glutamate-cysteine ligase in PC12 cells via activation of phospha-tidylinositol 3-kinase and Nrf2 signaling. J Biol Chem. 2007;282:28577-28586.
68. Jozkowicz A, Huk I, Nigisch A, Weigel G, Dietrich W, Motterlini R, Dulak J. Heme oxygenase and angiogenic activity of endothelial cells: stimulation by carbon monoxide and inhibition by tin protoporphyrin-IX. Antioxid Redox Signal. 2003;5:155-162.
69. Li Volti G, Sacerdoti D, Sangras B, Vanella A, Mezentsev A, Scapagnini G, Falck JR, Abraham NG. Carbon monoxide signaling in promoting angiogenesis in human microvessel endothelial cells. Antioxid Redox Signal. 2005;7:704-710.
70. Meng D, Wang X, Chang Q, Hitron A, Zhang Z, Xu M, Chen G, Luo J, Jiang B, Fang J, Shi X. Arsenic promotes angiogenesis in vitro via a heme oxygenase-1-dependent mechanism. Toxicol Appl Pharmacol. 2010;244:291-299.
71. Duckers HJ, Boehm M, True AL, Yet SF, San H, Park JL, Clinton Webb R, Lee ME, Nabel GJ, Nabel EG. Heme oxygenase-1 protects against vascular constriction and proliferation. Nat Med. 2001;7:693-698.
72. Dulak J, Jozkowicz A, Foresti R, Kasza A, Frick M, Huk I, Green CJ, Pachinger O, Weidinger F, Motterlini R. Heme oxygenase activity modulates vascular endothelial growth factor synthesis in vascular smooth muscle cells. Antioxid Redox Signal. 2002;4:229-240.
73. Jazwa A, Loboda A, Golda S, Cisowski J, Szelag M, Zagorska A, Sroczynska P, Drukala J, Jozkowicz A, Dulak J. Effect of heme and heme oxygenase-1 on vascular endothelial growth factor synthesis and angiogenic potency of human keratinocytes. Free Radic Biol Med. 2006;40:1250-1263.
74. Dulak J, Deshane J, Jozkowicz A, Agarwal A. Heme oxygenase-1 and carbon monoxide in vascular pathobiology: focus on angiogenesis. Circulation. 2008;117:231-241.
75. Cudmore M, Ahmad S, Al-Ani B, Fujisawa T, Coxall H, Chudasama K, Devey LR, Wigmore SJ, Abbas A, Hewett PW, Ahmed A. Negative regulation of soluble Flt-1 and soluble endoglin release by heme oxygenase-1. Circulation. 2007;115:1789-1797.
76. Cisowski J, Loboda A, Jozkowicz A, Chen S, Agarwal A, Dulak J. Role of heme oxygenase-1 in hydrogen peroxide-induced VEGF synthesis: effect of HO-1 knockout. Biochem Biophys Res Commun. 2005;326:670-676.
77. Fernandez M, Bonkovsky HL. Vascular endothelial growth factor increases heme oxygenase-1 protein expression in the chick embryo chorioallantoic membrane. Br J Pharmacol. 2003;139:634-640.
78. Bussolati B, Ahmed A, Pemberton H, Landis RC, Di Carlo F, Haskard DO, Mason JC. Bifunctional role for VEGF-induced heme oxygenase-1 in vivo: induction of angiogenesis and inhibition of leukocytic infiltration. Blood. 2004;103:761-766.
79. Bussolati B, Mason JC. Dual role of VEGF-induced heme-oxygenase-1 in angiogenesis. Antioxid Redox Signal. 2006;8:1153-1163.
80. Torisu-Itakura H, Furue M, Kuwano M, Ono M. Co-expression of thymidine phosphorylase and heme oxygenase-1 in macrophages in human malignant vertical growth melanomas. Jpn J Cancer Res. 2000;91:906-910.
81. Sunamura M, Duda DG, Ghattas MH, Lozonschi L, Motoi F, Yamauchi J, Matsuno S, Shibahara S, Abraham NG. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer. Angiogenesis. 2003;6:15-24.
82. Hirai K, Sasahira T, Ohmori H, Fujii K, Kuniyasu H. Inhibition of heme oxygenase-1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL mice. Int J Cancer. 2007;120:500-505.
83. Marinissen MJ, Tanos T, Bolos M, de Sagarra MR, Coso OA, Cuadrado A. Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor. J Biol Chem. 2006;281:11332-11346.
84. Martin MJ, Tanos T, Garcia AB, Martin D, Gutkind JS, Coso OA, Marinissen MJ. The Galpha12/13 family of heterotrimeric G proteins and the small GTPase RhoA link the Kaposi sarcoma-associated herpes virus G protein-coupled receptor to heme oxygenase-1 expression and tumorigenesis. J Biol Chem. 2007;282:34510-34524.
85. Kim EH, Na HK, Surh YJ. Upregulation of VEGF by 15-deoxy-Delta12,14-prostaglandin J2 via heme oxygenase-1 and ERK1/2 signaling in MCF-7 cells. Ann N Y Acad Sci. 2006;1090:375-384.
86. Kim DH, Kim JH, Kim EH, Na HK, Cha YN, Chung JH, Surh YJ. 15-Deoxy-Delta12,14-prostaglandin J2 up-regulates the expression of heme oxygenase-1 and subsequently matrix metalloproteinase-1 in human breast cancer cells: possible roles of iron and ROS. Carcinogenesis. 2009;30:645-654.
87. Rundhaug JE. Matrix metalloproteinases and angiogenesis. J Cell Mol Med. 2005;9:267-285.
88. Morita K, Lee MS, Her S. Possible relation of hemin-induced HO-1 expression to the upregulation of VEGF and BDNF mRNA levels in rat C6 glioma cells. J Mol Neurosci. 2009;38:31-40.
89. Was H, Cichon T, Smolarczyk R, Rudnicka D, Stopa M, Chevalier C, Leger JJ, Lackowska B, Grochot A, Bojkowska K, Ratajska A, Kieda C, Szala S, Dulak J, Jozkowicz A. Overexpression of heme oxygenase-1 in murine melanoma: increased proliferation and viability of tumor cells, decreased survival of mice. Am J Pathol. 2006;169:2181-2198.
90. Shibuya A, Onda K, Kawahara H, Uchiyama Y, Nakayama H, Omi T, Nagaoka M, Matsui H, Hirano T. Sofalcone, a gastric mucosa protective agent, increases vascular endothelial growth factor via the Nrf2-heme-oxygenase-1 dependent pathway in gastric epithelial cells. Biochem Biophys Res Commun. 2010;398:581-584.
91. Kweider N, Fragoulis A, Rosen C, Pecks U, Rath W, Pufe T, Wruck CJ. Interplay between vascular endothelial growth factor (VEGF) and nuclear factor erythroid 2-related factor-2 (Nrf2): implications for preeclampsia. J Biol Chem. 2011;286:42863-42872.
92. Hockel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst. 2001;93:266-276.
93. Hockel M, Vaupel P. Biological consequences of tumor hypoxia. Semin Oncol. 2001;28(Suppl 8):36-41.
94. Harris AL. Hypoxia--a key regulatory factor in tumour growth. Nat Rev Cancer. 2002;2:38-47.
95. Greco O, Marples B, Joiner MC, Scott SD. How to over-come (and exploit) tumor hypoxia for targeted gene therapy. J Cell Physiol. 2003;197:312-325.
96. Ruas JL, Poellinger L, Pereira T. Role of CBP in regulating HIF-1-mediated activation of transcription. J Cell Sci. 2005;118(Pt 2):301-311.
97. Nordgren IK, Tavassoli A. Targeting tumour angiogenesis with small molecule inhibitors of hypoxia inducible factor. Chem Soc Rev. 2011;40:4307-4317.
98. Talks KL, Turley H, Gatter KC, Maxwell PH, Pugh CW, Ratcliffe PJ, Harris AL. The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol. 2000;157:411-421.
99. Turner KJ, Moore JW, Jones A, Taylor CF, Cuthbert-Heavens D, Han C, Leek RD, Gatter KC, Maxwell PH, Ratcliffe PJ, Cranston D, Harris AL. Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation. Cancer Res. 2002;62:2957-2961.
100. Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene. 2010;29:625-634.
101. Maltepe E, Schmidt JV, Baunoch D, Bradfield CA, Simon MC. Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nature. 1997;386:403-407.
102. Ryan HE, Lo J, Johnson RS. HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J. 1998;17:3005-3015.
103. Tomita S, Ueno M, Sakamoto M, Kitahama Y, Ueki M, Maekawa N, Sakamoto H, Gassmann M, Kageyama R, Ueda N, Gonzalez FJ, Takahama Y. Defective brain development in mice lacking the Hif-1alpha gene in neural cells. Mol Cell Biol. 2003;23:6739-6749.
104. Tang N, Wang L, Esko J, Giordano FJ, Huang Y, Gerber HP, Ferrara N, Johnson RS. Loss of HIF-1alpha in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell. 2004;6:485-495.
105. Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996;16:4604-4613.
106. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669-676.
107. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011-1027.
108. Kong D, Park EJ, Stephen AG, Calvani M, Cardellina JH, Monks A, Fisher RJ, Shoemaker RH, Melillo G. Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. Cancer Res. 2005;65:9047-9055.
109. Zhang H, Qian DZ, Tan YS, Lee K, Gao P, Ren YR, Rey S, Hammers H, Chang D, Pili R, Dang CV, Liu JO, Semenza GL. Digoxin and other cardiac glycosides inhibit HIF-1alpha synthesis and block tumor growth. Proc Natl Acad Sci U S A. 2008;105:19579-19586.
110. Lee K, Qian DZ, Rey S, Wei H, Liu JO, Semenza GL. Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cells. Proc Natl Acad Sci U S A. 2009;106:2353-2358.
111. Loboda A, Stachurska A, Florczyk U, Rudnicka D, Jazwa A, Wegrzyn J, Kozakowska M, Stalinska K, Poellinger L, Levonen AL, Yla-Herttuala S, Jozkowicz A, Dulak J. HIF-1 induction attenuates Nrf2-dependent IL-8 expression in human endothelial cells. Antioxid Redox Signal. 2009;11:1501-1517.
112. Florczyk U, Czauderna S, Stachurska A, Tertil M, Nowak W, Kozakowska M, Poellinger L, Jozkowicz A, Loboda A, Dulak J. Opposite effects of HIF-1alpha and HIF-2alpha on the regulation of IL-8 expression in endothelial cells. Free Radic Biol Med. 2011;51:1882-1892.
113. Li A, Dubey S, Varney ML, Dave BJ, Singh RK. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J Immunol. 2003;170:3369-3376.
114. Singh RK, Varney ML. IL-8 expression in malignant melanoma: implications in growth and metastasis. Histol Histopathol. 2000;15:843-849.
115. Fujimoto J, Sakaguchi H, Aoki I, Tamaya T. Clinical implications of expression of interleukin 8 related to angiogenesis in uterine cervical cancers. Cancer Res. 2000;60:2632-2635.
116. Li A, Varney ML, Singh RK. Expression of interleukin 8 and its receptors in human colon carcinoma cells with different metastatic potentials. Clin Cancer Res. 2001;7:3298-3304.
117. Matsuo Y, Ochi N, Sawai H, Yasuda A, Takahashi H, Funahashi H, Takeyama H, Tong Z, Guha S. CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote invasiveness and angiogenesis in pancreatic cancer. Int J Cancer. 2009;124:853-861.
118. Vegran F, Boidot R, Michiels C, Sonveaux P, Feron O. Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-kappaB/IL-8 pathway that drives tumor angiogenesis. Cancer Res. 2011;71:2550-2560.
119. Chen RJ, Chen SU, Chou CH, Lin MC. Lysophosphatidic acid receptor 2/3-mediated IL-8-dependent angiogenesis in cervical cancer cells. Int J Cancer. 2012;131:789-802.
120. Zhang X, Chen X, Song H, Chen HZ, Rovin BH. Activation of the Nrf2/antioxidant response pathway increases IL-8 expression. Eur J Immunol. 2005;35:3258-3267.
121. Schetter AJ, Nguyen GH, Bowman ED, Mathe EA, Yuen ST, Hawkes JE, Croce CM, Leung SY, Harris CC. Association of inflammation-related and microRNA gene expression with cancer-specific mortality of colon adenocarcinoma. Clin Cancer Res. 2009;15:5878-5887.
122. Maxwell PJ, Gallagher R, Seaton A, Wilson C, Scullin P, Pettigrew J, Stratford IJ, Williams KJ, Johnston PG, Waugh DJ. HIF-1 and NF-kappaB-mediated upregulation of CXCR1 and CXCR2 expression promotes cell survival in hypoxic prostate cancer cells. Oncogene. 2007;26:7333-7345.
123. Ferrando M, Gueron G, Elguero B, Giudice J, Salles A, Leskow FC, Jares-Erijman EA, Colombo L, Meiss R, Navone N, De Siervi A, Vazquez E. Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer. Angiogenesis. 2011;14:467-479.
124. De Marzo AM, Nakai Y, Nelson WG. Inflammation, atrophy, and prostate carcinogenesis. Urol Oncol. 2007;25:398-400.