Cancer and Metastasis Reviews

, Volume 23, Issue 1–2, pp 63–75 | Cite as

Role of cyclooxygenase-2 in colorectal cancer

Article

Abstract

Cyclooxygenase-2 (COX-2) is an inducible enzyme that regulates prostaglandin synthesis and is overexpressed at sites of inflammation and in several epithelial cancers. Recently, a causal link for COX-2 in epithelial tumorigenesis was shown in genetically-manipulated animal models of colon and breast carcinoma. Data indicate that COX-2 is involved in the regulation of apoptosis, angiogenesis, and tumor cell invasiveness, which appear to contribute to its effects on tumorigenesis. Multiple studies have shown that nonselective COX and selective COX-2 inhibitors effectively prevent experimental colon cancer. Furthermore, sulindac and the selective COX-2 inhibitor celecoxib were shown to regress colorectal polyps in patients with familial adenomatous polyposis. Although the exact anti-tumor mechanisms of these agents await further study, data indicate that both COX-dependent and COX-independent mechanisms may be important. In this review, the association between COX-2 and colorectal tumorigenesis and potential mechanisms of this effect are discussed. Additionally, evidence supporting the role of NSAIDs and selective COX-2 inhibitors for the prevention and treatment of human colorectal cancer is reviewed.

cyclooxygenase-2 colorectal cancer NSAIDs tumorigenesis coxibs 

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References

  1. 1.
    Jemal AT, Murray A, Samuels A, Ghafoor E, Ward, Thun MJ: Cancer statistics, 2003. CA Cancer J Clin 53(1): 5–26, 2003Google Scholar
  2. 2.
    Thun MJ, Namboodiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325(23): 1593–1596, 1991Google Scholar
  3. 3.
    Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC: Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med 121(4): 241–246, 1994Google Scholar
  4. 4.
    Giovannucci E, Egan KM, Hunter DJ, Stampfer MJ, Colditz GA, Willett WC, Speizer FE: Aspirin and the risk of colorectal cancer in women. N Engl J Med 333(10): 609–614, 1995Google Scholar
  5. 5.
    Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN: Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107(4): 1183–1188, 1994Google Scholar
  6. 6.
    DuBois RN, Radhika A, Reddy BS, Entingh AJ: Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors. Gastroenterology 110(4): 1259–1262, 1996Google Scholar
  7. 7.
    Williams CS, Luongo C, Radhika A, Zhang T, Lamps LW, Nanney LB, Beauchamp RD, DuBois RN: Elevated cyclooxygenase-2 levels in Min mouse adenomas. Gastroenterology 111(4): 1134–1140, 1996Google Scholar
  8. 8.
    Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, Trzaskos JM, Evans JF, Taketo MM: Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87(5): 803–809, 1996Google Scholar
  9. 9.
    Kawamori T, Rao CV, Seibert K, Reddy BS: Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 58(3): 409–412, 1998Google Scholar
  10. 10.
    Jacoby RF, Marshall DJ, Newton MA, Novakovic K, Tutsch K, Cole CE, Lubet RA, Kelloff GJ, Verma A, Moser AR, Dove WF: Chemoprevention of spontaneous intestinal adenomas in the Apc Min mouse model by the nonsteroidal anti-inflammatory drug piroxicam. Cancer Res 56(4): 710–714, 1996Google Scholar
  11. 11.
    Mahmoud NN, Boolbol SK, Dannenberg AJ, Mestre JR, Bilinski RT, Martucci C, Newmark HL, Chadburn A, Bertagnolli MM: The sulfide metabolite of sulindac prevents tumors and restores enterocyte apoptosis in a murine model of familial adenomatous polyposis. Carcinogenesis 19(1): 87–91, 1998Google Scholar
  12. 12.
    Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, Booker SV, Robinson CR, Offerhaus GJ: Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 328(18): 1313–1316, 1993Google Scholar
  13. 13.
    Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342(26): 1946–1952, 2000Google Scholar
  14. 14.
    Feldman M, McMahon AT: Do cyclooxygenase-2 inhibitors provide benefits similar to those of traditional nonsteroidal anti-inflammatory drugs, with less gastrointestinal toxicity? Ann Intern Med 132(2): 134–143, 2001Google Scholar
  15. 15.
    Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 343(21): 1520–1528, 2000Google Scholar
  16. 16.
    Smith WL, DeWitt DL, Garavito RM: Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69: 145–182, 2000Google Scholar
  17. 17.
    Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE: Cyclooxygenase in biology and disease. Faseb J 12(12): 1063–1073, 1998Google Scholar
  18. 18.
    Herschman HR, Xie W, Reddy S: Inflammation, reproduction, cancer and all that. The regulation and role of the inducible prostaglandin synthase. Bioessays 17(12): 1031–1037, 1995Google Scholar
  19. 19.
    Herschman HR: Prostaglandin synthase 2. Biochim Biophys Acta 1299(1): 125–140, 1996Google Scholar
  20. 20.
    Xie WL, Chipman JG, Robertson DL, Erikson RL, Simmons DL: Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci USA 88(7): 2692–2696, 1991Google Scholar
  21. 21.
    Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR: TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 266(20): 12866–12872, 1991Google Scholar
  22. 22.
    Hla T, Neilson K: Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci USA 89(16): 7384–7388, 1992Google Scholar
  23. 23.
    Soslow RA, Dannenberg AJ, Rush D, Woerner BM, Khan KN, Masferrer J, Koki AT: COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 89(12): 2637–2645, 2000Google Scholar
  24. 24.
    FitzGerald GA, Patrono C: The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 345(6): 433–442, 2001Google Scholar
  25. 25.
    Marnett LJ, Kalgutkar AS: Cyclooxygenase 2 inhibitors: Discovery, selectivity and the future. Trends Pharmacol Sci 20(11): 465–469, 1999Google Scholar
  26. 26.
    Sinicrope FA, Lemoine M, Xi L, Lynch PM, Cleary KR, Shen Y, Frazier ML: Reduced expression of cyclooxygenase 2 proteins in hereditary nonpolyposis colorectal cancers relative to sporadic cancers. Gastroenterology 117(2): 350–358, 1999Google Scholar
  27. 27.
    Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M, Hla T: Expression of cyclooxygenase-1 and-2 in human colorectal cancer. Cancer Res 55(17): 3785–3789, 1995Google Scholar
  28. 28.
    Kargman SL, O'Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S: Expression of prostaglandin G/H synthase-1 and-2 protein in human colon cancer. Cancer Res 55(12): 2556–2559, 1995Google Scholar
  29. 29.
    Bamba H, Ota S, Kato A, Adachi A, Itoyama S, Matsuzaki F: High expression of cyclooxygenase-2 in macrophages of human colonic adenoma. Int J Cancer 83(4): 470–475, 1999Google Scholar
  30. 30.
    Chapple KS, Cartwright EJ, Hawcroft G, Tisbury A, Bonifer C, Scott N, Windsor AC, Guillou PJ, Markham AF, Coletta PL, Hull MA: Localization of cyclooxygenase-2 in human sporadic colorectal adenomas. Am J Pathol 156(2): 545–553, 2000Google Scholar
  31. 31.
    Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ, Seibert K: Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 60(5): 1306–1311, 2000Google Scholar
  32. 32.
    Ristimaki A, Sivula A, Lundin J, Lundin M, Salminen T, Haglund C, Joensuu H, Isola J: Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 62(3): 632–635, 2002Google Scholar
  33. 33.
    Half E, Tang XM, Gwyn K, Sahin A, Wathen K, Sinicrope FA: Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ. Cancer Res 62(6): 1676–1681, 2002Google Scholar
  34. 34.
    Molina MA, Sitja-Arnau M, Lemoine MG, Frazier ML, Sinicrope FA: Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: Growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res 59(17): 4356–4362, 1999Google Scholar
  35. 35.
    Tucker ON, Dannenberg AJ, Yang EK, Zhang F, Teng L, Daly JM, Soslow RA, Masferrer JL, Woerner BM, Koki AT, Fahey TJ: 3rd, Cyclooxygenase-2 expression is upregulated in human pancreatic cancer. Cancer Res 59(5): 987–990, 1999Google Scholar
  36. 36.
    Lord RV, Danenberg KD, Danenberg PV: Cyclooxygenase-2 in Barrett's esophagus, Barrett's adenocarcinomas, and esophageal SCC: Ready for clinical trials. Am J Gastroenterol 94(8): 2313–2315, 1999Google Scholar
  37. 37.
    Shamma A, Yamamoto H, Doki Y, Okami J, Kondo M, Fujiwara Y, Yano M, Inoue M, Matsuura N, Shiozaki H, Monden M: Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus. Clin Cancer Res 6(4): 1229–1238, 2000Google Scholar
  38. 38.
    van Rees BP, Saukkonen K, Ristimaki A, Polkowski W, Tytgat GN, Drillenburg P, Offerhaus GJ: Cyclooxygenase-2 expression during carcinogenesis in the human stomach. J Pathol 196(2): 171–179, 2002Google Scholar
  39. 39.
    Yamagata R, Shimoyama T, Fukuda S, Yoshimura T, Tanaka M, Munakata A: Cyclooxygenase-2 expression is increased in early intestinal-type gastric cancer and gastric mucosa with intestinal metaplasia. Eur J Gastroenterol Hepatol 14(4): 359–363, 2002Google Scholar
  40. 40.
    Wolff H, Saukkonen K, Anttila S, Karjalainen A, Vainio H, Ristimaki A: Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 58(22): 4997–5001, 1998Google Scholar
  41. 41.
    Shao J, Sheng H, Aramandla R, Pereira MA, Lubet RA, Hawk E, Grogan L, Kirsch IR, Washington MK, Beauchamp RD, DuBois RN: Coordinate regulation of cyclooxygenase-2 and TGF-beta1 in replication errorpositive colon cancer and azoxymethane-induced rat colonic tumors. Carcinogenesis 20(2): 185–191, 1999Google Scholar
  42. 42.
    Hull M, Langman M: Differential expression of cyclooxygenase 2 in human colorectal cancer. Gut 47(1): 154, 2000Google Scholar
  43. 43.
    Shattuck-Brandt RL, Varilek GW, Radhika A, Yang F, Washington MK, DuBois RN: Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice. Gastroenterology 118(2): 337–345, 2000Google Scholar
  44. 44.
    Williams CS, Tsujii M, Reese J, Dey SK, DuBois RN: Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest 105(11): 1589–1594, 2000Google Scholar
  45. 45.
    Sonoshita M, Takaku K, Oshima M, Sugihara K, Taketo MM: Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps. Cancer Res 62(23): 6846–6849, 2002Google Scholar
  46. 46.
    Karnes WE, Jr. Shattuck-Brandt R, Burgart LJ, DuBois RN, Tester DJ, Cunningham JM, Kim CY, McDonnell SK, Schaid DJ, Thibodeau SN: Reduced COX-2 protein in colorectal cancer with defective mismatch repair. Cancer Res 58(23): 5473–5477, 1998Google Scholar
  47. 47.
    Cunningham JM, Christensen ER, Tester DJ, Kim CY, Roche PC, Burgart LJ, Thibodeau SN: Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 58(15): 3455–3460, 1998Google Scholar
  48. 48.
    Toyota M, Shen L, Ohe-Toyota M, Hamilton SR, Sinicrope FA, Issa JP: Aberrant methylation of the Cyclooxygenase 2 CpG island in colorectal tumors. Cancer Res 60(15): 4044–4048, 2000Google Scholar
  49. 49.
    Toyota M, Ohe-Toyota M, Ahuja N, Issa JP: Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. Proc Natl Acad Sci USA 97(2): 710–715, 2000Google Scholar
  50. 50.
    Lal G, Ash C, Hay K, Redston M, Kwong E, Hancock B, Mak T, Kargman S, Evans JF, Gallinger S: Suppression of intestinal polyps in Msh2-deficient and non-Msh2-deficient multiple intestinal neoplasia mice by a specific cyclooxygenase-2 inhibitor and by a dual cyclooxygenase-1/2 inhibitor. Cancer Res 61(16): 6131–6136, 2001Google Scholar
  51. 51.
    Sheehan KM, Sheahan K, O'Donoghue DP, MacSweeney F, Conroy RM, Fitzgerald DJ, Murray FE: The relationship between cyclooxygenase-2 expression and colorectal cancer. Jama 282(13): 1254–1257, 1999Google Scholar
  52. 52.
    Pereira MA, Barnes LH, Rassman VL, Kelloff GV, Steele VE: Use of azoxymethane-induced foci of aberrant crypts in rat colon to identify potential cancer chemopreventive agents. Carcinogenesis 15(5): 1049–1054, 1994Google Scholar
  53. 53.
    Reddy BS, Hirose Y, Lubet R, Steele V, Kelloff G, Paulson S, Seibert K, Rao CV: Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. Cancer Res 60(2): 293–297, 2000Google Scholar
  54. 54.
    Boolbol SK, Dannenberg AJ, Chadburn A, Martucci C, Guo XJ, Ramonetti JT, Abreu-Goris M, Newmark HL, Lipkin ML, DeCosse JJ, Bertagnolli MM: Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res 56(11): 2556–2560, 1996Google Scholar
  55. 55.
    Jacoby RF, Seibert K, Cole CE, Kelloff G, Lubet RA: The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res 60(18): 5040–5044, 2000Google Scholar
  56. 56.
    Oshima M, Murai N, Kargman S, Arguello M, Luk P, Kwong E, Taketo MM, Evans JF: Chemoprevention of intestinal polyposis in the Apcdelta716 mouse by rofecoxib, a specific cyclooxygenase-2 inhibitor. Cancer Res 61(4): 1733–1740, 2001Google Scholar
  57. 57.
    Liu CH, Chang SH, Narko K, Trifan OC, Wu MT, Smith E, Haudenschild C, Lane TF, Hla T: Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 276(21): 18563–18569, 2001Google Scholar
  58. 58.
    Neufang G, Furstenberger G, Heidt M, Marks F, Muller-Decker K: Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin. Proc Natl Acad Sci USA 98(13): 7629–7634, 2001Google Scholar
  59. 59.
    Bedi A, Pasricha PJ, Akhtar AJ, Barber JP, Bedi GC, Giardiello FM, Zehnbauer BA, Hamilton SR, Jones RJ: Inhibition of apoptosis during development of colorectal cancer. Cancer Res 55(9): 1811–1816, 1995Google Scholar
  60. 60.
    Sinicrope FA, Roddey G, McDonnell TJ, Shen Y, Cleary KR, Stephens LC: Increased apoptosis accompanies neoplastic development in the human colorectum. Clin Cancer Res 2(12): 1999–2006, 1996Google Scholar
  61. 61.
    Moss SF, Scholes JV, Holt PR: Abnormalities of epithelial apoptosis in multistep colorectal neoplasia demonstrated by terminal deoxyuridine nick end labeling. Dig Dis Sci 41(11): 2238–2247, 1996Google Scholar
  62. 62.
    Tsujii M, DuBois RN: Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83(3): 493–501, 1995Google Scholar
  63. 63.
    Sun Y, Tang XM, Half E, Kuo MT, Sinicrope FA: Cyclooxygenase-2 overexpression reduces apoptotic susceptibility by inhibiting the cytochrome c-dependent apoptotic pathway in human colon cancer cells. Cancer Res 62(21): 6323–6328, 2002Google Scholar
  64. 64.
    Tang X, Sun YJ, Half E, Kuo MT, Sinicrope F: Cyclooxygenase-2 overexpression inhibits death receptor 5 expression and confers resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human colon cancer cells. Cancer Res 62(17): 4903–4908, 2002Google Scholar
  65. 65.
    He Q, Luo X, Huang Y, Sheikh MS: Apo2L/TRAIL differentially modulates the apoptotic effects of sulindac and a COX-2 selective non-steroidal anti-inflammatory agent in Bax-deficient cells. Oncogene 21(39): 6032–6040, 2002Google Scholar
  66. 66.
    Shattuck-Brandt RL, Lamps LW, Heppner Goss KJ, DuBois RN, Matrisian LM: Differential expression of matrilysin and cyclooxygenase-2 in intestinal and colorectal neoplasms. Mol Carcinog 24(3): 177–187, 1999Google Scholar
  67. 67.
    Tsujii M, Kawano S, DuBois RN: Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci USA 94(7): 3336–3340, 1997Google Scholar
  68. 68.
    Li G, Yang T, Yan J: Cyclooxygenase-2 increased the angiogenic and metastatic potential of tumor cells. Biochem Biophys Res Commun 299(5): 886–886, 2002Google Scholar
  69. 69.
    Attiga FA, Fernandez PM, Weeraratna AT, Manyak MJ, Patierno SR: Inhibitors of prostaglandin synthesis inhibit human prostate tumor cell invasiveness and reduce the release of matrix metalloproteinases. Cancer Res 60(16): 4629–4637, 2000Google Scholar
  70. 70.
    Peterson HI: Effects of prostaglandin synthesis inhibitors on tumor growth and vascularization. Experimental studies in the rat. Invasion Metastasis 3(3): 151–159, 1983Google Scholar
  71. 71.
    Jones MK, Wang H, Peskar BM, Levin E, Itani RM, Sarfeh IJ, Tarnawski AS: Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: Insight into mechanisms and implications for cancer growth and ulcer healing. Nat Med 5(12): 1418–1423, 1999Google Scholar
  72. 72.
    Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN: Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93(5): 705–716, 1998Google Scholar
  73. 73.
    Majima M, Hayashi I, Muramatsu M, Katada J, Yamashina S, Katori M: Cyclo-oxygenase-2 enhances basic fibroblast growth factor-induced angiogenesis through induction of vascularendothelialgrowthfactor in ratspongeimplants.Br J Pharmacol 130(3): 641–649, 2000Google Scholar
  74. 74.
    Cianchi F, Cortesini C, Bechi P, Fantappie O, Messerini L, Vannacci A, Sardi I, Baroni G, Boddi V, Mazzanti R, Masini E: Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer. Gastroenterology 121(6): 1339–1347, 2001Google Scholar
  75. 75.
    Daniel TO, Liu H, Morrow JD, Crews BC, Marnett LJ: Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis. Cancer Res 59(18): 4574–4577, 1999Google Scholar
  76. 76.
    Chulada PC, Thompson MB, Mahler JF, Doyle CM, Gaul BW, Lee C, Tiano HF, Morham SG, Smithies O, Langenbach R: Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res 60(17): 4705–4708, 2000Google Scholar
  77. 77.
    Elder DJ, Halton DE, Hague A, Paraskeva C: Induction of apoptotic cell death in human colorectal carcinoma cell lines by a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug: Independence from COX-2 protein expression Clin Cancer Res 3(10): 1679–1683, 1997Google Scholar
  78. 78.
    Sheng H, Shao J, Kirkland SC, Isakson P, Coffey RJ, Morrow J, Beauchamp RD, DuBois RN: Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest 99(9): 2254–2259, 1997Google Scholar
  79. 79.
    Shiff SJ, Qiao L, Tsai LL, Rigas B: Sulindac sulfide, an aspirin-like compound, inhibits proliferation, causes cell cycle quiescence, and induces apoptosis in HT-29 colon adenocarcinoma cells. J Clin Invest 96(1): 491–503, 1995Google Scholar
  80. 80.
    Piazza GA, Rahm AL, Krutzsch M, Sperl G, Paranka NS, Gross PH, Brendel K, Burt RW, Alberts DS, Pamukcu R, et al.: Antineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing apoptosis. Cancer Res 55(14): 3110–3116, 1995Google Scholar
  81. 81.
    Williams CS, Watson AJ, Sheng H, Helou R, Shao J, DuBois RN: Celecoxib prevents tumor growth in vivo without toxicity to normal gut: Lack of correlation between in vitro and in vivo models. Cancer Res 60(21): 6045–6051, 2000Google Scholar
  82. 82.
    Samaha HS, Kelloff GJ, Steele V, Rao CV, Reddy BS: Modulation of apoptosis by sulindac, curcumin, phenylethyl-3-methylcaffeate, and 6-phenylhexyl isothiocyanate: Apoptotic index as a biomarker in colon cancer chemoprevention and promotion. Cancer Res 57(7): 1301–1305, 1997Google Scholar
  83. 83.
    Keller JJ, Offerhaus GJ, Polak M, Goodman SN, Zahurak ML, Hylind LM, Hamilton SR, Giardiello FM: Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with sulindac. Gut 45(6): 822–828, 1999Google Scholar
  84. 84.
    Sinicrope FA, Half E, Lynch PM, Morrow J, Levin B, Ayers G, Morris J, Hawk E, Stephens LC: Cell proliferation and apoptotic indices predict adenoma regression in a placebo-controled trial of celecoxib in familial adenomatous polyposis (FAP) Patients. Proc of Digestive Diseases Week, 2003Google Scholar
  85. 85.
    Zhang L, Yu J, Park BH, Kinzler KW, Vogelstein B: Role of BAX in the apoptotic response to anticancer agents. Science 290(5493): 989–992, 2000Google Scholar
  86. 86.
    Hanif R, Pittas A, Feng Y, Koutsos MI, Qiao L, Staiano-Coico L, Shiff SI, Rigas B: Effects of nonsteroidal antiin flammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandinindependent pathway. Biochem Pharmacol 52(2): 237–245, 1996Google Scholar
  87. 87.
    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 190(4): 451–459, 1999Google Scholar
  88. 88.
    Coffey RJ, Hawkey CJ, Damstrup L, Graves-Deal R, Daniel VC, Dempsey PJ, Chinery R, Kirkland SC, DuBois RN, Jetton TL, Morrow JD: 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 94(2): 657–662, 1997Google Scholar
  89. 89.
    Elder DJ, Halton DE, Crew TE, Paraskeva C: Apoptosis induction and cyclooxygenase-2 regulation in human colorectal adenoma and carcinoma cell lines by the cyclooxygenase-2-selective non-steroidal anti-inflammatory drug NS-398. Int J Cancer 86(4): 553–560, 2000Google Scholar
  90. 90.
    Piazza GA, Alberts DS, Hixson LJ, Paranka NS, Li H, Finn T, Bogert C, Guillen JM, Brendel K, Gross PH, Sperl G, Ritchie J, Burt RW, Ellsworth L, Ahnen DJ, Pamukcu R: Sulindac sulfone inhibits azoxymethaneinduced colon carcinogenesis in rats without reducing prostaglandin levels. Cancer Res 57(14): 2909–2915, 1997Google Scholar
  91. 91.
    Alberts DS, Hixson L, Ahnen D, Bogert C, Einspahr J, Paranka N, Brendel K, Gross PH, Pamukcu R, Burt RW: Do NSAIDs exert their colon cancer chemoprevention activities through the inhibition of mucosal prostaglandin synthetase? J Cell Biochem Suppl 22: 18–23, 1995Google Scholar
  92. 92.
    Kopp E, Ghosh S: Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 265(5174): 956–959, 1994Google Scholar
  93. 93.
    Yamamoto Y, Yin MJ, Lin KM, Gaynor RB: Sulindac inhibits activation of the NF-kappaB pathway. J Biol Chem 274(38): 27307–27314, 1999Google Scholar
  94. 94.
    Yin MJ, Yamamoto Y, Gaynor RB: The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 396(6706): 77–80, 1998Google Scholar
  95. 95.
    Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA: Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem 272(6): 3406–3410, 1997Google Scholar
  96. 96.
    He TC, Chan TA, Vogelstein B, Kinzler KW: PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell 99(3): 335–345, 1999Google Scholar
  97. 97.
    Park BH, Vogelstein B, Kinzler KW: Genetic disruption of PPARdelta decreases the tumorigenicity of human colon cancer cells. Proc Natl Acad Sci USA 98(5): 2598–2603, 2001Google Scholar
  98. 98.
    Harris RE, Namboodiri KK, Farrar WB: Nonsteroidal antiinflammatory drugs and breast cancer. Epidemiology 7(2): 203–205, 1996Google Scholar
  99. 99.
    Sharpe CR, Collet JP, McNutt M, Belzile E, Boivin JF, Hanley JA: Nested case-control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage. Br J Cancer 83(1): 112–120, 2000Google Scholar
  100. 100.
    Egan KM, Stampfer MJ, Giovannucci E, Rosner BA, Colditz GA: Prospective study of regular aspirin use and the risk of breast cancer. J Natl Cancer Inst 88(14): 988–993, 1996Google Scholar
  101. 101.
    Ferrandina G, Lauriola L, Zannoni GF, Fagotti A, Fanfani F, Legge F, Maggiano N, Gessi M, Mancuso S, Ranelletti FO, Scambia G: Increased cyclooxygenase-2 (COX-2) expression is associated with chemotherapy resistance and outcome in ovarian cancer patients. Ann Oncol 13(8): 1205–1211, 2002Google Scholar
  102. 102.
    Khuri FR, Wu H, Lee JJ, Kemp BL, Lotan R, Lippman SM, Feng L, Hong WK, Xu XC: Cyclooxygenase-2 overexpression is a marker of poor prognosis in stage I non-small cell lung cancer. Clin Cancer Res 7(4): 861–867, 2001Google Scholar
  103. 103.
    Buskens CJ, Van Rees BP, Sivula A, Reitsma JB, Haglund C, Bosma PJ, Offerhaus GJ, Van Lanschot JJ, Ristimaki A: Prognostic significance of elevated cyclooxygenase 2 expression in patients with adenocarcinoma of the esophagus. Gastroenterology 122(7): 1800–1807, 2002Google Scholar
  104. 104.
    Liu XH, Rose DP: Differential expression and regulation of cyclooxygenase-1 and-2 in two human breast cancer cell lines. Cancer Res 56(22): 5125–5127, 1996Google Scholar
  105. 105.
    Subbaramaiah K, Norton L, Gerald W, Dannenberg AJ: Cyclooxygenase-2 is overexpressed in HER-2/neu-positive breast cancer: Evidence for involvement of AP-1 and PEA3. J Biol Chem 277(21): 18649–18657, 2002Google Scholar
  106. 106.
    Howe LR, Subbaramaiah K, Patel J, Masferrer JL, Deora A, Hudis C, Thaler HT, Muller WJ, Du B, Brown AM, Dannenberg AJ: Celecoxib, a selective cyclooxygenase 2 inhibitor, protects against human epidermal growth factor receptor 2 (HER-2)/neu-induced breast cancer. Cancer Res 62(19): 5405–5407, 2002Google Scholar
  107. 107.
    Waddell WR, Ganser GF, Cerise EJ, Loughry RW: Sulindac for polyposis of the colon. Am J Surg 157(1): 175–179, 1989Google Scholar
  108. 108.
    Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS: Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: The CLASS study: A randomized controled trial. Celecoxib Longterm Arthritis Safety Study. JAMA 284(10): 1247–1255, 2000Google Scholar
  109. 109.
    Bensen WG, Zhao SZ, Burke TA, Zabinski RA, Makuch RW, Maurath CJ, Agrawal NM, Geis GS: Upper gastrointestinal tolerability of celecoxib, a COX-2 specific inhibitor, compared to naproxen and placebo. J Rheumatol 27(8): 1876–1883, 2000Google Scholar
  110. 110.
    Goldstein JL, Silverstein FE, Agrawal NM, Hubbard RC, Kaiser J, Maurath CJ, Verburg KM, Geis GS: Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor. Am J Gastroenterol 95(7): 1681–1690, 2000Google Scholar
  111. 111.
    Watson DJ, Harper SE, Zhao PL, Quan H, Bolognese JA, Simon TJ: Gastrointestinal tolerability of the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib compared with nonselective COX-1 and COX-2 inhibitors in osteoarthritis. Arch Intern Med 160(19): 2998–3003, 2000Google Scholar
  112. 112.
    Laine L, Bombardier C, Hawkey CJ, Davis B, Shapiro D, Brett C, Reicin A: Stratifying the risk of NSAID-related upper gastrointestinal clinical events: Results of a doubleblind outcomes study in patients with rheumatoid arthritis. Gastroenterology 123(4): 1006–1012, 2002Google Scholar
  113. 113.
    Chan FK, Hung LC, Suen BY, Wu JC, Lee KC, Leung VK, Hui AJ, To KF, Leung WK, Wong VW, Chung SC, Sung JJ: Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med 347(26): 2104–2110, 2002Google Scholar
  114. 114.
    Ray WA, Stein CM, Daugherty JR, Hall K, Arbogast PG, Griffin MR: COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet 360(9339): 1071–1073, 2002Google Scholar
  115. 115.
    Mukherjee D, Nissen SE, Topol EJ: Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 286(8): 954–959, 2001Google Scholar
  116. 116.
    Mann M, Sheng H, Shao J, Williams CS, Pisacane PI, Sliwkowski MX, DuBois RN: Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth. Gastroenterology 120(7): 1713–1719, 2001Google Scholar
  117. 117.
    Yao M, Kargman S, Lam EC, Kelly CR, Zheng Y, Luk P, Kwong E, Evans JF, Wolfe MM: Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice. Cancer Res 63(3): 586–592, 2003Google Scholar
  118. 118.
    Trifan OC, Durham WF, Salazar VS, Horton J, Levine BD, Zweifel BS, Davis TW, Masferrer JL: Cyclooxygenase-2 inhibition with celecoxib enhances antitumor ef.-cacy and reduces diarrhea side effect of CPT-11. Cancer Res 62(20): 5778–5784, 2002Google Scholar
  119. 119.
    Sinicrope FA, Pazdur R, Levin B: Phase I trial of sulindac plus 5-fluorouracil and levamisole: Potential adjuvant therapy for colon carcinoma. Clin Cancer Res 2(1): 37–41, 1996Google Scholar
  120. 120.
    Blanke CD, Benson AB, Dragovich T, Lenz H, Haller D, Robles C, Buchbinder A: A phase II trial of celecoxib, irinotecan, 5-fluorouracil and leucovorin in patients with unresectable or metastatic colorectal cancer. in Proc Am Soc of Clin Onc, 2002Google Scholar
  121. 121.
    Kishi K, Petersen S, Petersen C, Hunter N, Mason K, Masferrer JL, Tofilon PJ, Milas L: Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res 60(5): 1326–1331, 2000Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  1. 1.Mayo ClinicDivision of Gastroenterology and Hepatology, Division of Medical OncologyRochester

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