Skip to main content
SpringerLink
Log in

Cyclooxygenase-2 Inhibitors and Colorectal Cancer Prevention

  • Chapter
Cancer Chemoprevention

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 246 Accesses

Abstract

Colorectal cancer (CRC) causes approx 550,000 deaths worldwide each year, and is a major public health concern in most industrialized regions of the globe (1). Once an individual is diagnosed with CRC, the disease is often advanced and treatment regimens are mostly ineffective and highly toxic. Alternative cytotoxic regimens are being developed which hold some promise for improved treatment responses (2). Recently, selective cyclooxygenase-2 (COX-2) inhibitors have been evaluated for prevention or treatment of colorectal cancer. This chapter will review some of the key findings from both the laboratory and the clinic that have led to the hypothesis that COX-2 selective inhibitors may be useful in cancer prevention or treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin 2000;50:7–33.

    Article  PubMed  CAS  Google Scholar 

  2. Rothenberg ML. Irinotecan (CPT-11): recent developments and future directions colorectal cancer and beyond. Oncologist 2001;6:66–80.

    Article  PubMed  CAS  Google Scholar 

  3. Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 2000;69:145–182.

    Article  PubMed  CAS  Google Scholar 

  4. Kanai N, Lu R, Satriano JA, et al. Identification and characterization of a prostaglandin transporter. Science 1995;268:866–869.

    Article  PubMed  CAS  Google Scholar 

  5. DuBois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB J 1998;12:1063–1073.

    PubMed  CAS  Google Scholar 

  6. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature 1971;231:232–235.

    CAS  Google Scholar 

  7. Isakson P, Seibert K, Masferrer J, et al. Discovery of a better aspirin. Adv Prostaglandins Thromboxane Leukot Res 1995;23:49–54.

    CAS  Google Scholar 

  8. Masferrer JL, Zweifel BS, Manning PT, et al. Selective inhibition of inducible cyclooxygenase-2 in vivo is antiinflammatory and nonulcerogenic. Proc Nall Acad Sci USA 1994;91:3228–3232.

    Article  CAS  Google Scholar 

  9. Harris RC, Breyer MD. Physiological regulation of cyclooxygenase-2 in the kidney. Am J Physiol Renal Physiol 2001;281:F1-F11.

    PubMed  CAS  Google Scholar 

  10. Kurumbail RG, Stevens AM, Gierse JK, et al. Structural basis for selective inhibition of cyclooxygenase-2 by antiinflammatory agents. Nature 1996;384:644–648.

    Article  PubMed  CAS  Google Scholar 

  11. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal antiinflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000;284:1247–1255.

    Article  PubMed  CAS  Google Scholar 

  12. Bombardier C. An evidence-based evaluation of the gastrointestinal safety of coxibs. Am J Cardiol 2002;89:3D-9D.

    Article  PubMed  CAS  Google Scholar 

  13. Kalgutkar A, Crews B, Rowlinson S, et al. Aspirin-like molecules that covalently inactivate cyclooxygenase-2. Science 1998;280:1268–1270.

    Article  PubMed  CAS  Google Scholar 

  14. Smalley W, DuBois RN. Colorectal cancer and non steroidal antiinflammatory drugs. Adv Pharmacol 1997;39:1–20.

    Article  PubMed  CAS  Google Scholar 

  15. Rigas B, Goldman IS, Levine L. Altered eicosanoid levels in human colon cancer. J Lab Clin Med 1993;122:518–523.

    PubMed  CAS  Google Scholar 

  16. Qiao L, Kozoni V, Tsioulias GJ, et al. Selected eicosanoids increase the proliferation rate of human colon carcinoma cell lines and mouse colonocytes in vivo. Biochem Biophys Acta 1995;1258:215–223.

    Article  PubMed  Google Scholar 

  17. 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.

    PubMed  CAS  Google Scholar 

  18. Kargman S, O’Neill G, Vickers P, et al. Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res 1995;55:2556–2559.

    PubMed  CAS  Google Scholar 

  19. Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in APCΔ7 16 knockout mice by inhibition of prostaglandin endoperoxide synthase-2 (COX-2). Cell 1996;87:803–809.

    Article  PubMed  CAS  Google Scholar 

  20. Liu HL, Chang SH, Narko K, et al. Over-expression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 2001;276:18,563–18,569.

    CAS  Google Scholar 

  21. 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.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    PubMed  CAS  Google Scholar 

  23. Masferrer JL, Leahy KM, Koki AT, et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 Inhibitors. Cancer Res 2000;60:1306–1311.

    PubMed  CAS  Google Scholar 

  24. Williams CS, Tsujii M, Reese J, et al. Host cyclooxygenase-2 modulates carcinoma growth. J Clin Investig 2000;105:1589–1594.

    Article  PubMed  CAS  Google Scholar 

  25. Zhang X, Morham SG, Langenbach R, Young DA. Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase-null embryo fibroblasts. J Exp Med 1999;190:445–450.

    Article  Google Scholar 

  26. Yin MJ, Yamamoto Y, Gaynor RB. The antiinflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 1998;396:77–80.

    Article  PubMed  CAS  Google Scholar 

  27. Lehmann JM, Lenhard JM, Oliver BB, et al. Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal antiinflammatory drugs. J Biol Chem 1997;272:3406–3410.

    Article  PubMed  CAS  Google Scholar 

  28. Yamamoto Y, Yin MJ, Lin KM, Gaynor RB. Sulindac inhibits activation of the NF-kappaB pathway. J Biol Chem 1999;274:27,307–27,314.

    CAS  Google Scholar 

  29. Zhang L, Yu J, Park BH, et al. Role of BAX in the apoptotic response to anticancer agents. Science 2000;290:989–992.

    Article  PubMed  CAS  Google Scholar 

  30. Williams CS, Watson AJ, Sheng H, et al. Celecoxib prevents tumor growth in vivo without toxicity to normal gut: lack of correlation between in vitro and in vivo models. Cancer Res 2000;60:6045–6051.

    PubMed  CAS  Google Scholar 

  31. Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase-2. Cell 1995;83:493–501.

    Article  PubMed  CAS  Google Scholar 

  32. Tsujii M, Kuwano S, DuBois RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Nall Acad Sci USA 1997;94:3336–3340.

    Article  CAS  Google Scholar 

  33. Tsujii M, Kawano S, Tsuji S, et al. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998;93:705–716.

    Article  PubMed  CAS  Google Scholar 

  34. Majima M, Isono M, Ikeda Y, et al. Significant roles of inducible cyclooxygenase (COX)-2 in angiogenesis in rat sponge implants. Jpn J Pharmacol 1997;75:105–114.

    Article  PubMed  CAS  Google Scholar 

  35. Majima M, Hayashi I, Muramatsu M, et al. Cyclo-oxygenase-2 enhances basic fibroblast growth factor-induced angiogenesis through induction of vascular endothelial growth factor in rat sponge implants. Br J Pharmacol 2000;130:641–649.

    Article  PubMed  CAS  Google Scholar 

  36. Daniel TO, Liu H, Morrow JD, et al. Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis. Cancer Res 1999;59:4574–4577.

    PubMed  CAS  Google Scholar 

  37. Jones MK, Wang H, Peskar BM, et al. Inhibition of angiogenesis by nonsteroidal antiinflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing. Nat Med 1999;5:1418–1423.

    Article  PubMed  CAS  Google Scholar 

  38. Dormond O, Foletti A, Paroz C, Ruegg C. NSAIDs inhibit alpha V beta 3 integrin-mediated and Cdc42/Rac-dependent endothelial-cell spreading, migration and angiogenesis. Nat Med 2001;7:1041–1047.

    Article  PubMed  CAS  Google Scholar 

  39. Sugimoto Y, Narumiya S, Ichikawa A. Distribution and function of prostanoid receptors: studies from knockout mice. Prog Lipid Res 2000; 39:289–314.

    Article  PubMed  CAS  Google Scholar 

  40. Morita I, Schindler M, Regier MK, et al. Different intracellular locations for prostaglandin endoperoxide H synthase-1 and -2. J Biol Chem 1995;270:10,902–10,908.

    CAS  Google Scholar 

  41. Bhattacharya M, Peri KG, Almazan G, et al. Nuclear localization of prostaglandin E2 receptors. Proc Natl Acad Sci USA 1998;95:15,792–15,797.

    Article  CAS  Google Scholar 

  42. Giardiello FM, Spannhake EW, DuBois RN, et al. Prostaglandin levels in human colorectal mucosa: effect of sulindac in patients with familial adenomatous polyposis (FAP). Gastroenterology 1997;112:A568.

    Article  Google Scholar 

  43. Sheng H, Shao J, Morrow J, et al. Modulation of apoptosis by prostaglandin treatment in human colon cancer cells. Cancer Res 1998;58:362–366.

    PubMed  CAS  Google Scholar 

  44. Sheng H, Shao J, Washington MK, DuBois RN. Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem 2001;276:18,075–18,081.

    CAS  Google Scholar 

  45. Adam L, Mazumdar A, Sharma T, et al. A three-dimensional and temporo-spatial model to study invasiveness of cancer cells by heregulin and prostaglandin E2. Cancer Res 2001;61:81–87.

    PubMed  CAS  Google Scholar 

  46. Watanabe K, Kawamori T, Nakatsugi S, et al. Inhibitory effect of a prostaglandin E receptor subtype EP(1) selective antagonist, ONO-8713, on development of azoxymethaneinduced aberrant crypt foci in mice. Cancer Lett 2000;156:57–61.

    Article  PubMed  CAS  Google Scholar 

  47. Watanabe K, Kawamori T, Nakatsugi S, et al. Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis. Cancer Res 1999;59:5093–5096.

    PubMed  CAS  Google Scholar 

  48. Sonoshita M, Takaku K, Sasaki N, et al. Acceleration of intestinal polyposis through prostaglandin receptor EP2 in ApcDelta716 knockout mice. Nat Med 2001;7:1048–1051.

    Article  PubMed  CAS  Google Scholar 

  49. DuBois RN, Giardiello FM, Smalley WE. Nonsteroidal antiinflammatory drugs, eicosanoids and colorectal cancer prevention. Gastroenterol Clin N Am 1996;25:773–791.

    Article  CAS  Google Scholar 

  50. Paganini-Hill A, Hsu G, Ross RK, Henderson BE. Aspirin use and incidence of large-bowel cancer in a California retirement community. J Natl Cancer Inst 1991;83:1182–1183.

    Article  PubMed  CAS  Google Scholar 

  51. Waddell WR, Loughry RW. Sulindac for polyposis of the colon. J Surg Oncol 1983;24:83–87.

    Article  PubMed  CAS  Google Scholar 

  52. Giardiello FM, Hamilton SR, Krush AJ, et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 1993;328:1313–1316.

    Article  PubMed  CAS  Google Scholar 

  53. 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.

    Article  PubMed  CAS  Google Scholar 

  54. Matsuhashi N, Nakajima A, Shinohara K, et al. Rectal cancer after sulindac therapy for a sporadic adenomatous colonic polyp. Am J Gastroenterol 1998;93:2261–2266.

    Article  PubMed  CAS  Google Scholar 

  55. Giardiello FM, Yang VW, Hylind LM, et al. Primary chemoprevention of familial adenomatous polyposis with sulindac. N Engl J Med 2002;346:1054–1059.

    Article  PubMed  CAS  Google Scholar 

  56. Baron JA, Beach M, Mandel JS, et al. Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group. N Engl J Med 1999;340:101–107.

    Article  PubMed  CAS  Google Scholar 

  57. Torrance CJ, Jackson PE, Montgomery E, et al. Combinatorial chemoprevention of intestinal neoplasia. Nat Med 2000;6:1024–1028.

    Article  PubMed  CAS  Google Scholar 

  58. Mann M, Sheng H, Shao J, et al. Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth. Gastroenterology 2001;120:1713–1719.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Raymond N. DuBois MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. National Institutes of Health, Rockville, MD, USA

    Gary J. Kelloff MD  & Ernest T. Hawk MD, MPH  & 

  2. CCS Associates, Mountain View, CA, USA

    Caroline C. Sigman PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

DuBois, R.N. (2004). Cyclooxygenase-2 Inhibitors and Colorectal Cancer Prevention. In: Kelloff, G.J., Hawk, E.T., Sigman, C.C. (eds) Cancer Chemoprevention. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-767-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-767-3_6

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-342-8

  • Online ISBN: 978-1-59259-767-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation