European Journal of Cancer
Volume 41, Issue 13 , Pages 1854-1863 , September 2005

Cyclooxygenase-2: How good is it as a target for cancer chemoprevention?

  • Mark A. Hull

      Affiliations

    • Corresponding Author InformationTel.: +44 113 206 5251; fax: +44 113 242 9722.

Received 24 March 2005 ,Accepted 1 April 2005.

References 

  1. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol. 1998;38:97–120
  2. Herschman HR. Prostaglandin synthase 2. Biochim Biophys Acta. 1996;1299:125–140
  3. Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294:1871–1875
  4. Gupta RA, DuBois RN. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer. 2001;1:11–21
  5. Diaz BL, Arm JP. Phospholipase A2. Prostag Leukotr Ess. 2003;69:87–97
  6. Reddy ST, Herschman HR. Ligand-induced prostaglandin synthesis requires expression of the TIS10/PGS-2 prostaglandin synthase gene in murine fibroblasts and macrophages. J Biol Chem. 1994;269:15473–15480
  7. Chulada PC, Thompson MB, Mahler JF, et al. Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res. 2000;60:4705–4708
  8. Fitzgerald GA. COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat Rev Drug Discov. 2003;2:879–890
  9. Chandrasekharan NV, Dai H, Turepu Roos KL, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci USA. 2002;99:13926–13931
  10. Helliwell RJA, Adams LF, Mitchell MD. Prostaglandin synthases: recent developments and a novel hypothesis. Prostag Leukotr Ess. 2004;70:101–113
  11. Murakami M, Nakatani Y, Tanioka T, et al. Prostaglandin E synthase. Prostag Oth Lipid M. 2002;68–69:383–399
  12. Narumiya S, Fitzgerald GA. Genetic and pharmacological analysis of prostanoid receptor function. J Clin Invest. 2001;108:25–30
  13. Gupta RA, DuBois RN. Controversy: PPARγ as a target for treatment of colorectal cancer. Am J Physiol Gastrointest Liver Physiol. 2002;283:G266–G269
  14. Lim H, Dey SK. A novel pathway of prostacyclin signaling – hanging out with nuclear receptors. Endocrinology. 2002;143:3207–3210
  15. Yan M, Rerko RM, Platzer P, et al. 15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-β-induced suppressor of human gastrointestinal cancers. Proc Natl Acad Sci USA. 2004;101:17468–17473
  16. Backlund MG, Mann JR, Holla VR, et al. 15-hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer. J Biol Chem. 2005;280:3217–3223
  17. Thun MJ, Henley SJ, Patrono C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst. 2002;94:252–266
  18. Fosslien E. Biochemistry of cyclooxygenase (COX)-2 inhibitors and molecular pathology of COX-2 in neoplasia. Crit Rev Clin Lab Sci. 2000;37:431–502
  19. Dannenberg AJ, Altorki NK, Boyle JO, et al. Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol. 2001;2:544–551
  20. Dannenberg AJ, Subbaramaiah K. Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cell. 2003;4:431–436
  21. Shirvani VN, Ouatu-Lascar R, Kaur BS, et al. Cycloxygenase 2 expression in Barrett’s esophagus and adenocarcinoma: ex vivo induction by bile salts and acid exposure. Gastroenterology. 2000;118:487–496
  22. Sung JJY, Leung WK, Go MYY, et al. Cyclooxygenase-2 expression in Helicobacter pylori-associated premalignant and malignant gastric lesions. Am J Pathol. 2000;157:729–735
  23. Cheng AS, Chan HL, Leung WK, et al. Expression of HBx and COX-2 in chronic hepatitis B, cirrhosis and hepatocellular carcinoma: implication of HBx in upregulation of COX-2. Mod Pathol. 2004;17:1169–1179
  24. Schlosser W, Schlosser S, Ramadani M, et al. Cyclooxygenase-2 is overexpressed in chronic pancreatitis. Pancreas. 2002;25:26–30
  25. Hayashi N, Yamamoto H, Hiraoka N, et al. Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm. Hepatology. 2001;34:638–650
  26. Wendum D, Svrcek M, Rigau V, et al. COX-2, inflammatory secreted PLA2 and cytoplasmic PLA2 protein expression in small bowel adenocarcinomas compared with colorectal adenocarcinomas. Mod Pathol. 2003;16:130–136
  27. Chapple KS, Scott N, Guillou PJ, et al. Analysis of cyclooxygenase expression in human colorectal adenomas. Dis Colon Rectum. 2002;1316–1324
  28. Agoff SN, Brentnall TA, Crispin DA, et al. The role of cyclooxygenase 2 in ulcerative colitis-associated neoplasia. Am J Pathol. 2000;157:737–745
  29. Wang W, Bergh A, Damber JE. Chronic inflammation in benign prostate hyperplasia is associated with focal upregulation of cyclooxygenase-2, Bcl-2, and cell proliferation in the glandular epithelium. Prostate. 2004;61:60–72
  30. El-Sheikh SS, Madaan S, Albasso A, et al. Cyclooxygenase-2: a possible target in schistosoma-associated bladder cancer. BJU Int. 2001;88:921–927
  31. Sudbo J, Reith A. Which putatively pre-malignant oral lesions become oral cancers? Clinical relevance of early targeting of high-risk individuals. J Oral Pathol Med. 2003;32:63–70
  32. Nijsten T, Colpaert CG, Vermeulen PB, et al. Cyclooxygenase-2 expression and angiogenesis in squamous cell carcinoma of the skin and its precursors: a paired immunohistochemical study of 35 cases. Br J Dermatol. 2004;151:837–845
  33. Buckman SY, Gresham A, Hale P, et al. COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer. Carcinogenesis. 1998;19:723–729
  34. Ardies CM. Inflammation as cause for scar cancers of the lung. Integr Cancer Ther. 2003;2:238–246
  35. Boland GP, Butt IS, Prasad R, et al. COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ. Br J Cancer. 2004;90:423–429
  36. Tazawa R, Xu X-M, Wu KK, et al. Characterization of the genomic structure, chromosomal location and promoter of human prostaglandin H synthase-2 gene. Biochem Biophys Res Commun. 1994;203:190–199
  37. Chun K-S, Surh Y-J. Signal transduction pathways regulating cyclooxygenase-2 expression: potential molecular targets for chemoprevention. Biochem Pharmacol. 2004;68:1089–1100
  38. Subbaramaiah K, Norton L, Gerald W, et al. Cyclooxygenase-2 is overexpressed in HER-2/neu-positive breast cancer: evidence for involvement of AP-1 and PEA3. J Biol Chem. 2002;277:18649–18657
  39. Sheng H, Shao J, DuBois RN. K-Ras-mediated increase in cyclooxygenase 2 mRNA stability involves activation of the protein kinase B1. Cancer Res. 2001;61:2670–2675
  40. Araki Y, Okamura S, Hussain SP, et al. Regulation of cyclooxygenase-2 expression by the Wnt and Ras pathways. Cancer Res. 2003;63:728–734
  41. Subbaramaiah K, Altorki N, Chung WJ, et al. Inhibition of cyclooxygenase-2 gene expression by p53. J Biol Chem. 1999;274:10911–109115
  42. Hwang D, Jang BC, Yu G, et al. Expression of mitogen-inducible cyclooxygenase induced by lipopolysaccharide. Biochem Pharmacol. 1997;54:87–96
  43. Mestre JR, Mackrell PJ, Rivadeneira DE, et al. Redundancy in the signalling pathways and promoter elements regulating cyclooxygenase-2 gene expression in endotoxin-treated macrophage/monocytic cells. J Biol Chem. 2001;276:3977–3982
  44. Gorgoni B, Caivano M, Arizmendi C, et al. The transcription factor C/EBPβ is essential for inducible expression of the cox-2 gene in macrophages but not in fibroblasts. J Biol Chem. 2001;276:40769–40777
  45. Sengupta S, Jang BC, Wu M-T, et al. The RNA-binding protein HuR regulates the expression of cyclooxygenase-2. J Biol Chem. 2003;278:25227–25233
  46. Wendum D, Masliah J, Trugnan G, et al. Cyclooxygenase-2 and its role in colorectal cancer development. Virchows Archiv. 2004;445:327–333
  47. Kojima M, Morisaki T, Izuhara K, et al. Lipopolysaccharide increases cyclo-oxygenase-2 expression in a colon carcinoma cell line through nuclear factor-κB activation. Oncogene. 2000;19:1225–1231
  48. Glinghammar B, Rafter J. Colonic luminal contents induce cyclooxygenase 2 transcription in human colon carcinoma cells. Gastroenterology. 2001;120:401–410
  49. Tucker ON, Dannenberg AJ, Yang EK, et al. Bile acids induce cyclooxygenase-2 expression in human pancreatic cancer cell lines. Carcinogenesis. 2004;25:419–423
  50. Zhang F, Altorki NK, Wu YC, et al. Duodenal reflux induces cyclooxygenase-2 in the esophageal mucosa of rats: evidence for involvement of bile acids. Gastroenterology. 2001;121:1391–1399
  51. Chang YJ, Wu MS, Sheu BS, et al. Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and Src-dependent nuclear factor-kappaB activation. Mol Pharmacol. 2004;66:1465–1477
  52. Inaba T, Sano H, Kawahito Y, et al. Induction of cyclooxygenase-2 in monocyte/macrophage by mucins secreted from colon cancer cells. Proc Natl Acad Sci USA. 2003;100:2736–2741
  53. Coffey RJ, Hawkey CJ, Damstrup L, et al. Epidermal growth factor receptor activation induces nuclear targeting of cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cells. Proc Natl Acad Sci USA. 1997;94:657–662
  54. Ko SCW, Chapple KS, Hawcroft G, et al. Paracrine cyclooxygenase-2-mediated signalling by macrophages promotes tumorigenic progression of intestinal epithelial cells. Oncogene. 2002;21:7175–7186
  55. Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase-2. Cell. 1995;83:493–501
  56. Tsujii M, Kawano S, DuBois RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci USA. 1997;94:3336–3340
  57. Fosslien E. Molecular pathology of cyclooxygenase-2 in cancer-induced angiogenesis. Ann Clin Lab Sci. 2001;31:325–348
  58. Stolina M, Sharma S, Lin Y, et al. Specific inhibition of cyclooxygenase-2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis. J Immunol. 2000;164:361–370
  59. Sharma RA, Gescher A, Plastaras JP, et al. Cyclooxygenase-2, malondialdehyde and pyrimidopurinone adducts of deoxyguanosine in human colon cells. Carcinogenesis. 2001;22:1557–1560
  60. Marnett LJ. Prostaglandin synthase-mediated metabolism of carcinogens and a potential role for peroxyl radicals as reactive intermediates. Environ Health Persp. 1990;88:5–12
  61. Wiese FW, Thompson PA, Kadlubar FF. Carcinogen substrate specificity of human COX-1 and COX-2. Carcinogenesis. 2001;21:5–10
  62. Liu CH, Chang S-H, Narko K, et al. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem. 2001;276:18563–18569
  63. Neufang G, Furstenberger G, Heidt M, et al. Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin. Proc Natl Acad Sci USA. 2001;98:7629–7634
  64. Oshima H, Oshima M, Inaba K, et al. Hyperplastic gastric tumors induced by activated macrophages in COX-2/mPGES-1 transgenic mice. EMBO J. 2004;23:1669–1678
  65. Chang S-H, Liu CH, Conway R, et al. Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proc Natl Acad Sci USA. 2004;101:591–596
  66. Buchanan FG, Chang W, Sheng H, et al. Up regulation of the enzymes involved in prostacyclin synthesis via Ras induces vascular endothelial growth factor. Gastroenterology. 2004;127:1391–1400
  67. Fukuda R, Kelly B, Semenza GL. Vascular endothelial growth factor gene expression in colon cancer cells exponed to prostaglandin E2 is mediated by hypoxia-inducible factor 1. Cancer Res. 2003;63:2330–2334
  68. Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in ApcΔ716 knockout mice by inhibition of prostaglandin endoperoxide synthase-2 (COX-2). Cell. 1996;87:803–809
  69. Hull MA, Ko SCW, Hawcroft G. Prostaglandin EP receptors: targets for treatment and prevention of colorectal cancer?. Mol Cancer Ther. 2004;3:1–9
  70. Tiano HF, Loftin CD, Akunda J, et al. Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. Cancer Res. 2002;62:3395–3401
  71. Dandekar AS, Lokeshwar BL. Inhibition of cyclooxygenase (COX)-2 expression by Tet-inducible COX-2 antisense cDNA in hormone-refractory prostate cancer cells significantly slows tumor growth and improves efficacy of chemotherapeutic drugs. Clin Cancer Res. 2004;10:8037–8047
  72. Buttar NS, Wang KK, Leontovich O, et al. Chemoprevention of esophageal adenocarcinomas by COX-2 inhibitors in an animal model of Barrett’s esophagus. Gastroenterology. 2002;122:1101–1112
  73. Hu PJ, Yu J, Zeng ZR, et al. Chemoprevention of gastric cancer by celecoxib in rats. Gut. 2004;53:195–200
  74. Wei M, Morimura K, Wanibuchi H, et al. Chemopreventative effect of JTE-522, a selective cyclooxygenase-2 inhibitor, in 2-dimethylhydrazine-induced rat colon carcinogenesis. Cancer Lett. 2003;202:11–16
  75. Furukawa F, Nishikawa A, Lee IS, et al. A cyclooxygenase-2 inhibitor, nimesulide, inhibits post-initiation phase of nitrobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamsters. Int J Cancer. 2003;104:269–273
  76. Narayanan BA, Narayanan NK, Pittman B, et al. Regression of mouse prostatic intra-epithelial neoplasia by nonsteroidal anti-inflammatory drugs in the transgenic adenocarcinoma mouse prostate model. Clin Cancer Res. 2004;10:7727–7737
  77. Gupta S, Adhami VM, Subbarayan M, et al. Suppression of prostate carcinogenesis by dietary supplementation of celecoxib in transgenic adenocarcinomas of the mouse prostate model. Cancer Res. 2004;64:3334–3343
  78. Yamamoto K, Kitayama W, Denda A, et al. Inhibitory effects of selective cyclooxygenase-2 inhibitors, nimesulide and etodolac, on the development of squamous cell dysplasias and carcinoma of the tongue in rats initiated with 4-nitroquinolone 1-oxide. Cancer Lett. 2003;199:121–129
  79. Nishimura N, Urade M, Hashitani S, et al. Increased expression of cyclooxygenase (COX)-2 in DMBA-induced hamster cheek pouch carcinogenesis and chemopreventative effect of a selective COX-2 inhibitor celecoxib. J Oral Pathol Med. 2004;33:614–621
  80. Wilgus TA, Koki AT, Zweifel BS, et al. Chemotherapeutic efficacy of topical celecoxib in a murine model of ultraviolet light B-induced skin cancer. Mol Carcinog. 2003;38:33–39
  81. Harris RE, Alshafie GA, Abou-Issa H, et al. Chemoprevention of breast cancer in rats by celecoxib, a cyclooxygenase-2 inhibitor. Cancer Res. 2000;60:2101–2103
  82. Nakatsugi S, Ohta T, Kawamori T, et al. Chemoprevention by nimesulide, a selective cyclooxygenase-2 inhibitor, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary gland carcinogenesis in rats. Jpn J Cancer Res. 2000;91:886–892
  83. Hwang DH, Fung V, Dannenberg AJ. National Cancer Institute workshop on chemopreventive properties of nonsteroidal anti-inflammatory drugs: role of COX-dependent and -independent mechanisms. Neoplasia. 2002;4:91–97
  84. Rahme E, Barkun AN, Toubouti Y, et al. The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence. Gastroenterology. 2004;125:404–412
  85. Bardou M, Barkun AN, Ghosn J, et al. Effect of chronic intake of NSAIDs and cyclooxygenase-2-selective inhibitors on esophageal cancer incidence. Clin Gastroenterol Hepatol. 2004;2:880–887
  86. Song X, Lin H-P, Johnson AJ, et al. Cyclooxygenase-2, player or spectator in cyclooxygenase-2 inhibitor-induced apoptosis in prostate cancer cells. J Natl Cancer Inst. 2002;94:585–591
  87. Arico S, Pattingre S, Bauvy C, et al. Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line. J Biol Chem. 2002;277:27613–27621
  88. Steinbach G, Lynch PM, Phillips RKS, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med. 2000;342:1946–1952
  89. Higuchi T, Iwama T, Yoshinaga K, et al. A randomized, double-blind, placebo-controlled trial of the effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on rectal polyps in familial adenomatous polyposis patients. Clin Cancer Res. 2003;9:4756–4760
  90. Hallak A, Alon-Baron L, Shamir R, et al. Rofecoxib reduces polyp recurrence in familial polyposis. Dig Dis Sci. 2003;48:1998–2002
  91. Hawk ET, Umar A, Viner JL. Colorectal cancer chemoprevention – an overview of the science. Gastroenterology. 2004;126:1423–1447
  92. http://cancer.gov/clinical_trials.
  93. http://www.ncri.org.uk/includes/icrp.htm.
  94. Morris CD, Armstrong GR, Bigley G, et al. Cyclooxygenase-2 expression in the Barrett’s metaplasia–dysplasia–adenocarcinoma sequence. Am J Gastroenterol. 2001;96:990–996
  95. Kitamura T, Itoh M, Noda T, et al. Combined effects of cyclooxygenase-1 and cyclooxygenase-2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice. Int J Cancer. 2004;109:576–580
  96. Pentland AP, Scott G, VanBuskirk J, et al. Cyclooxygenase-1 deletion enhances apoptosis but does not protect against ultraviolet light-induced tumors. Cancer Res. 2004;64:5587–5591
  97. Hur C, Simon LS, Gazelle GS. The cost-effectiveness of aspirin versus cyclooxygenase-2-selective inhibitors for colorectal carcinoma chemoprevention in healthy individuals. Cancer. 2004;101:189–197
  98. Emery P, Zeidler H, Kvein TK, et al. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison. Lancet. 1999;354:2106–2111
  99. Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med. 2000;343:1520–1528
  100. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. JAMA. 2000;284:1247–1255
  101. Schnitzer TJ, Burmester GR, Mysler E, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the therapeutic arthritis research and gastrointestinal event trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet. 2004;364:665–674
  102. Juni P, Rutjes AW, Dieppe PA. Are selective COX-2 inhibitors superior to traditional non-steroidal anti-inflammatory drugs. Br Med J. 2002;324:1287–1288
  103. Hawkey CJ. Cyclooxygenase inhibition: between the devil and the deep blue sea. Gut. 2002;50(Suppl III):25–30
  104. Whelton A. COX-2-specific inhibitors and the kidney: effect on hypertension and oedema. J Hypertens. 2002;20(Suppl 6):S31–S35
  105. Solomon SD, McMurray JJV, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352:1071–1080
  106. Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005;352:1092–1102
  107. Nussmeier NA, Whelton AA, Brown MT, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med. 2005;352:1081–1091
  108. Fitzgerald GA. Coxibs and cardiovascular disease. N Engl J Med. 2004;351:1709–1711
  109. Warner TD, Giuliano F, Vojnovic I, et al. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Prc Natl Acad Sci USA. 1999;96:7563–7568
  110. Rigas B, Kashfi K. Nitric-oxide-donating NSAIDs as agents for cancer prevention. Trends Mol Med. 2004;10:324–330
  111. Whittle BJR. Cyclooxygenase and nitric oxide systems in the gut as therapeutic targets for safer anti-inflammatory drugs. Curr Opin Pharmacol. 2004;4:538–545
  112. Torrance CJ, Jackson PE, Montgomery E, et al. Combinatorial chemoprevention of intestinal neoplasia. Nat Med. 2000;6:974–975
  113. Laye JP, Gill JH. Phospholipase A2 expression in tumours: a target for therapeutic intervention. Drug Discov Today. 2003;8:710–716

PII: S0959-8049(05)00331-X

doi: 10.1016/j.ejca.2005.04.013

European Journal of Cancer
Volume 41, Issue 13 , Pages 1854-1863 , September 2005