Current Colorectal Cancer Reports

, Volume 2, Issue 2, pp 60–65

Chemoprevention of colorectal cancer by inhibition of cyclooxygenase-2 derived prostaglandin E2 signaling: Recent advances in basic biology

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Abstract

Experimental evidence collected over the past decade has revealed that targeting cyclooxygenase-2 (COX-2) may have some efficacy for chemoprevention of cancer. However, recent safety concerns over the long-term use of COX-2 selective inhibitors are prompting research aimed at identifying other specific targets downstream of COX-2. In this regard, several groups have found that NSAIDs and COX-2 selective inhibitors primarily reduce the production of prostaglandin (PG) E2, a biologically active lipid product of the COX-2 enzyme, which results in attenuation of PGE2 signaling in the tumor microenvironment. Therefore, a detailed understanding of the PGE2 signaling pathway in transformed cells is critical to help identify novel and safer targets for effective prevention and/or treatment of cancer. Here we review the recent advances in elucidating the molecular mechanisms by which PGE2 promotes carcinogenesis.

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References and Recommended Reading

  1. 1.
    Jemal A, Murray T, Ward E, et al.: Cancer statistics, 2005. CA Cancer J Clin 2005, 55:10–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Greenlee RT, Murray T, Bolden S, Wingo PA: Cancer statistics, 2000. CA Cancer J Clin 2005, 50:7–33.Google Scholar
  3. 3.
    Waddell WR, Loughry RW: Sulindac for polyposis of the colon. J Surg Oncol 1983, 24:83–87. First demonstration that NSAIDs can act as a chemopreventive agent in FAP patients.PubMedCrossRefGoogle Scholar
  4. 4.
    Thun MJ, Namboodiri MM, Heath CW Jr: Aspirin use and reduced risk of fatal colon cancer. New Engl J Med 1991, 325:1593–1596.PubMedCrossRefGoogle Scholar
  5. 5.
    Gupta RA, Dubois RN: Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 2001, 1:11–21.PubMedCrossRefGoogle Scholar
  6. 6.
    Eberhart CE, Coffey RJ, Radhika A, et al.: Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994, 107:1183–1188. First demonstration that COX-2 is selectively upregulated in colorectal cancers.PubMedGoogle Scholar
  7. 7.
    Hwang D, Scollard D, Byrne J, Levine E: Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst 1998, 90:455–460.PubMedCrossRefGoogle Scholar
  8. 8.
    Tsuji S, Kawano S, Sawaoka H, et al.: Evidences for involvement of cyclooxygenase-2 in proliferation of two gastrointestinal cancer cell lines. Prostaglandins Leukot Essent Fatty Acids 1996, 55:179–183.PubMedCrossRefGoogle Scholar
  9. 9.
    Tucker ON, Dannenberg AJ, Yang EK, et al.: Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res 1999, 59:987–990.PubMedGoogle Scholar
  10. 10.
    Mohammed SI, Knapp DW, Bostwick DG, et al.: Expression of cyclooxygenase-2 (COX-2) in human invasive transitional cell carcinoma (TCC) of the urinary bladder. Cancer Res 1999, 59:5647–5650.PubMedGoogle Scholar
  11. 11.
    Hida T, Yatabe Y, Achiwa H, et al.: Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res 1998, 58:3761–3764.PubMedGoogle Scholar
  12. 12.
    Solomon DH, Schneeweiss S, Glynn RJ, et al.: Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004, 109:2068–2073.PubMedCrossRefGoogle Scholar
  13. 13.
    Bombardier C, Laine L, Reicin A, et al.: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000, 343:1520–1528.PubMedCrossRefGoogle Scholar
  14. 14.
    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.PubMedCrossRefGoogle Scholar
  15. 15.
    Cheng Y, Austin SC, Rocca B, et al.: Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 2002, 296:539–541.PubMedCrossRefGoogle Scholar
  16. 16.
    Fitzgerald GA: Coxibs and cardiovascular disease. N Engl J Med 2004, 351:1709–1711.PubMedCrossRefGoogle Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    Wolfe MM, Lichtenstein DR, Singh G: Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. New Engl J Med 1999, 340:1888–1899. [Published erratum appears in N Engl J Med 1999, 341:548.]PubMedCrossRefGoogle Scholar
  19. 19.
    Halter F, Tarnawski AS, Schmassmann A, Peskar BM: Cyclooxygenase 2-implications on maintenance of gastric mucosal integrity and ulcer healing: controversial issues and perspectives. Gut 2001, 49:443–453.PubMedCrossRefGoogle Scholar
  20. 20.
    Takafuji VA, Evans A, Lynch KR, Roche JK: PGE(2) receptors and synthesis in human gastric mucosa: perturbation in cancer. Prostaglandins Leukot Essent Fatty Acids 2002, 66:71–81.PubMedCrossRefGoogle Scholar
  21. 21.
    Smith WL: The eicosanoids and their biochemical mechanisms of action. Biochem J 1989, 259:315–324.PubMedGoogle Scholar
  22. 22.
    Marnett LJ, DuBois RN: COX-2: a target for colon cancer prevention. Annu Rev Pharmacol Toxicol 2002, 42:55–80.PubMedCrossRefGoogle Scholar
  23. 23.
    Backlund MG, Mann JR, Holla VR, et al.: 15-Hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer. J Biol Chem 2005, 280:3217–3223.PubMedCrossRefGoogle Scholar
  24. 24.
    Yan M, Rerko RM, Platzer P, et al.: 15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-beta-induced suppressor of human gastrointestinal cancers. Proc Natl Acad Sci U S A 2004, 101:17468–17473.PubMedCrossRefGoogle Scholar
  25. 25.
    Rigas B, Goldman IS, Levine L: Altered eicosanoid levels in human colon cancer. J Lab Clin Med 1993, 122:518–523.PubMedGoogle Scholar
  26. 26.
    Giardiello FM, Casero RA Jr, Hamilton SR, et al.: Prostanoids, ornithine decarboxylase, and polyamines in primary chemoprevention of familial adenomatous polyposis. Gastroenterology 2004, 126:425–431.PubMedCrossRefGoogle Scholar
  27. 27.
    Hansen-Petrik MB, McEntee MF, Jull B, et al.: Prostaglandin E(2) protects intestinal tumors from nonsteroidal anti-inflammatory drug-induced regression in Apc(Min+) mice. Cancer Res 2002, 62:403–408. Direct evidence that PGE2 is the main prostaglandin responsible for promoting growth of intestinal tumor.PubMedGoogle Scholar
  28. 28.
    Wang D, Wang H, Shi Q, et al.: Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta. Cancer Cell 2004, 6:285–295.PubMedCrossRefGoogle Scholar
  29. 29.
    Narumiya S, Sugimoto Y, Ushikubi F: Prostanoid receptors: structures, properties, and functions. Physiol Rev 1999, 79:1193–1226.PubMedGoogle Scholar
  30. 30.
    Sonoshita M, Takaku K, Sasaki N, et al.: Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. Nature Medicine 2001, 7:1048–1051. First genetic evidence that EP2 receptor can promote intestinal tumorigenesis downstream of COX-2.PubMedCrossRefGoogle Scholar
  31. 31.
    Mutoh M, Watanabe K, Kitamura T, et al.: Involvement of prostaglandin E receptor subtype EP(4) in colon carcinogenesis. Cancer Research 2002, 62:28–32.PubMedGoogle Scholar
  32. 32.
    Watanabe K, Kawamori T, Nakatsugi S, et al.: Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis. Cancer Research 1999, 59:5093–5096.PubMedGoogle Scholar
  33. 33.
    Amano H, Hayashi I, Endo H, et al.: Host prostaglandin E (2)-EP3 signaling regulates tumor-associated angiogenesis and tumor growth. J Exp Med 2003, 197:221–232.PubMedCrossRefGoogle Scholar
  34. 34.
    Chang SH, Liu CH, Conway R, et al.: Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Pro Natl Acad Sci U S A 2004, 101:591–596.CrossRefGoogle Scholar
  35. 35.
    Sheng H, Shao J, Washington MK, DuBois RN: Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem 2001, 276:18075–18081.PubMedCrossRefGoogle Scholar
  36. 36.
    Buchanan FG, Wang D, Bargiacchi F, DuBois RN: Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal grow th factor receptor. J Biol Chem 2003, 278:35451–35457.PubMedCrossRefGoogle Scholar
  37. 37.
    Pai R, Soreghan B, Szabo IL, et al.: Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med 2002, 8:289–293.PubMedCrossRefGoogle Scholar
  38. 38.
    Tsujii M, Kawano S, Tsuji S, et al.: Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998, 93:705–716. [Published erratum appears in Cell 1998, 94:271.] First demonstration that COX-2 regulates tumor angiogensis.PubMedCrossRefGoogle Scholar
  39. 39.
    Hernandez GL, Volpert OV, Iniguez MA, et al.: Selective inhibition of vascular endothelial growth factormediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2. J Exp Med 2001, 193:607–620.PubMedCrossRefGoogle Scholar
  40. 40.
    Iniguez MA, Rodriguez A, Volpert OV, et al.: Cyclooxygenase- 2: a therapeutic target in angiogenesis. Trends Mol Med 2003, 9:73–78.PubMedCrossRefGoogle Scholar
  41. 41.
    Pai R, Szabo IL, Giap AQ, et al.: Nonsteroidal antiinf lammator y drugs inhibit re-epithelialization of wounded gastric monolayers by interfering with actin, Src, FAK, and tensin signaling. Life Sci 2001, 69:3055–3071.PubMedCrossRefGoogle Scholar
  42. 42.
    Salcedo R, Zhang X, Young HA, et al.: Angiogenic effects of prostaglandin E2 are mediated by up-regulation of CXCR4 on human microvascular endothelial cells. Blood 2003, 102:1966–1977.PubMedCrossRefGoogle Scholar
  43. 43.
    Wheeler-Jones C, Abu-Ghazaleh R, Cospedal R, et al.: Vascular endothelial growth factor stimulates prostacyclin production and activation of cytosolic phospholipase A2 in endothelial cells via p42/p44 mitogen-activated protein kinase. FEBS Letters 1997, 420:28–32.PubMedCrossRefGoogle Scholar
  44. 44.
    Shao J, Jung C, Liu C, Sheng H: Prostaglandin E2 stimulates the beta-catenin/T cell factor-dependent transcription in colon cancer. J Biol Chem 2005, 280:26565–26572. Along with Castellone et al. [45], this article shows that mitogenic effects of PGE2 on colon cancer cells are dependent on interaction between PGE2 and Wnt signaling.PubMedCrossRefGoogle Scholar
  45. 45.
    Castellone MD, Teramoto H, Williams BO, et al.: Prostaglandin E2 promotes colon cancer cell growth through a novel Gs-axin-β-catenin signaling axis. Science 2005, 310:1504–1510. Along with Shao et al. [44], this article shows that mitogenic effects of PGE2 on colon cancer cells are dependent on interaction between PGE2 and Wnt signaling.PubMedCrossRefGoogle Scholar
  46. 46.
    Forman BM, Chen J, Evans RM: The peroxisome proliferator- activated receptors: ligands and activators. Ann N Y Acad Sci 1996, 804:266–275.PubMedCrossRefGoogle Scholar
  47. 47.
    He TC, Chan TA, Vogelstein B, Kinzler KW: PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell 1999, 99:335–345.PubMedCrossRefGoogle Scholar
  48. 48.
    Gupta RA, Tan J, Krause WF, et al.: Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer. Pro Nat Acad Sci U S A 2000, 97:13275–13280.CrossRefGoogle Scholar
  49. 49.
    Gupta RA, Wang D, Katkuri S, et al.: Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth. Nat Med 2004, 10:245–247.PubMedCrossRefGoogle Scholar
  50. 50.
    Grover JK, Yadav S, Vats V, Joshi YK: Cyclo-oxygenase 2 inhibitors: emerging roles in the gut. Int J Colorectal Dis 2003, 18:279–291.PubMedGoogle Scholar

Copyright information

© Current Science Inc. 2006

Authors and Affiliations

  1. 1.Department of Medicine, Cell and Developmental Biology and Cancer BiologyVanderbilt University Medical Center and Vanderbilt-Ingram Cancer CenterNashvilleUSA

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