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Cyclooxygenase 2 and its Metabolites: Implications for Lung Cancer Therapy

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Apoptosis in Carcinogenesis and Chemotherapy

Abstract

The cyclooxygenase 2 (COX-2) and its downstream metabolite prostaglandins play an important role in lung cancer development, progression and metastasis. COX-2 and some of its metabolites have been regarded as markers for diagnosis and prognosis for lung cancer prevention and therapy. There is increasing evidence indicating that the inhibition of the expression or/and the activity of COX-2 can sensitize tumor cells to anti-tumor treatments by promoting apoptosis. Thus the development of selective COX-2 inhibitors has become a hot area in anti-cancer treatment. This chapter will summarize the current development in COX-2 and its metabolites in lung cancer and will particularly focus on the therapeutic value of COX-2 inhibition in lung cancer treatment.

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References

  • Adrain C, Martin SJ (2001) The mitochondrial apoptosome: a killer unleashed by the cytochrome seas. Trends Biochem Sci 26:390–397

    Google Scholar 

  • Alam M, Wang JH, Coffey JC, Qadri SS, O’Donnell A, Aherne T, Redmond HP (2007) Characterization of the effects of cyclooxygenase-2 inhibition in the regulation of apoptosis in human small and non-small cell lung cancer cell lines. Ann Surg Oncol 14:2678–2684

    PubMed  Google Scholar 

  • Antonakopoulos N, Karamanolis DG (2007) The role of NSAIDs in colon cancer prevention. Hepatogastroenterology 54:1694–1700

    PubMed  CAS  Google Scholar 

  • Baldwin AS (2001) Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J Clin Invest 107:241–246

    PubMed  CAS  Google Scholar 

  • Bazan NG, Fletcher BS, Herschman HR, Mukherjee PK (1994) Platelet-activating factor and retinoic acid synergistically activate the inducible prostaglandin synthase gene. Proc Natl Acad Sci U S A 91:5252–5256

    PubMed  CAS  Google Scholar 

  • Bharti AC, Aggarwal BB (2002) Nuclear factor-kappa B and cancer: its role in prevention and therapy. Biochem Pharmacol 64:883–888

    PubMed  CAS  Google Scholar 

  • Bren-Mattison Y, Meyer AM, Van Putten V, Li H, Kuhn K, Stearman R, Weiser-Evans M, Winn RA, Heasley LE, Nemenoff RA (2008) Antitumorigenic effects of peroxisome proliferator-activated receptor-gamma in non-small-cell lung cancer cells are mediated by suppression of cyclooxygenase-2 via inhibition of nuclear factor-kappaB. Mol Pharmacol 73:709–717

    PubMed  CAS  Google Scholar 

  • Brown JR, DuBois RN (2004) Cyclooxygenase as a target in lung cancer. Clin Cancer Res 10:4266s–4269s

    PubMed  CAS  Google Scholar 

  • Campa D, Zienolddiny S, Maggini V, Skaug V, Haugen A, Canzian F (2004) Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer. Carcinogenesis 25:229–2235

    Google Scholar 

  • Chang HC, Weng CF (2001) Cyclooxygenase-2 level and culture conditions influence NS398-induced apoptosis and caspase activation in lung cancer cells. Oncol Rep 8:1321–1325

    PubMed  CAS  Google Scholar 

  • Chen GG, Lee TW, Yip JH, Xu H, Lee IK, Mok TS, Warner TD, Yim AP (2006) Increased thromboxane B(2) levels are associated with lipid peroxidation and Bcl-2 expression in human lung carcinoma. Cancer Lett 234:193–198

    PubMed  CAS  Google Scholar 

  • Chen L, He Y, Huang H, Liao H, Wei W (2008a) Selective COX-2 inhibitor celecoxib combined with EGFR-TKI ZD1839 on non-small cell lung cancer cell lines: in vitro toxicity and mechanism study. Med Oncol. 25:161–171

    Google Scholar 

  • Chen XJ, Xiao W, Qu X, Zhou SY (2008b) NS-398 enhances the efficacy of gemcitabine against lung adenocarcinoma through up-regulation of p21WAF1 and p27KIP1 protein. Neoplasma 55:200–204

    Google Scholar 

  • Cloutier JF, Drouin R, Weinfeld M, O’Connor TR, Castonguay A (2001) Characterization and mapping of DNA damage induced by reactive metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) at nucleotide resolution in human genomic DNA. J Mol Biol 313:539–557

    PubMed  CAS  Google Scholar 

  • Csiki I, Morrow JD, Sandler A, Shyr Y, Oates J, Williams MK, Dang T, Carbone DP, Johnson DH (2005) Targeting cyclooxygenase-2 in recurrent non-small cell lung cancer: a phase II trial of celecoxib and docetaxel. Clin Cancer Res 11:6634–6640

    PubMed  CAS  Google Scholar 

  • Cuneo KC, Fu A, Osusky KL, Geng L (2007) Effects of vascular endothelial growth factor receptor inhibitor SU5416 and prostacyclin on murine lung metastasis. Anticancer Drugs 18:349–355

    PubMed  CAS  Google Scholar 

  • DeWitt DL, Meade EA (1993) Serum and glucocorticoid regulation of gene transcription and expression of the prostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes. Arch Biochem Biophys 306:94–102

    PubMed  CAS  Google Scholar 

  • Dohadwala M, Batra RK, Luo J, Lin Y, Krysan K, Pold M, Sharma S, Dubinett SM (2002) Autocrine/paracrine prostaglandin E2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD44 in cyclooxygenase-2-dependent invasion. J Biol Chem 277:50828–50833

    PubMed  CAS  Google Scholar 

  • Duan W, Zhang L (2006) Cyclooxygenase inhibitors not inhibit resting lung cancer A549 cell proliferation. Prostaglandins Leukot Essent Fatty Acids 74:317–321

    PubMed  CAS  Google Scholar 

  • Edelman MJ, Watson D, Wang X, Morrison C, Kratzke RA, Jewell S, Hodgson L, Mauer AM, Gajra A, Masters GA, Bedor M, Vokes EE, Green MJ (2008) Eicosanoid modulation in advanced lung cancer: cyclooxygenase-2 expression is a positive predictive factor for celecoxib + chemotherapy–Cancer and Leukemia Group B Trial 30203. J Clin Oncol 26:848–855

    PubMed  CAS  Google Scholar 

  • Ermert L, Dierkes C, Ermert M (2003) Immunohistochemical expression of cyclooxygenase isoenzymes and downstream enzymes in human lung tumors. Clin Cancer Res 9:1604–1610

    PubMed  CAS  Google Scholar 

  • Everts B, Wahrborg P, Hedner T (2000) COX-2-Specific inhibitors–the emergence of a new class of analgesic and anti-inflammatory drugs. Clin Rheumatol 19:331–343

    PubMed  CAS  Google Scholar 

  • Fang KM, Shu WH, Chang HC, Wang JJ, Mak OT (2004) Study of prostaglandin receptors in mitochondria on apoptosis of human lung carcinoma cell line A549. Biochem Soc Trans 32:1078–1080

    PubMed  CAS  Google Scholar 

  • Fujimura M, Kasahara K, Shirasaki H, Heki U, Iwasa K, Ueda A, Matsuda T (1999) Up-regulation of ICH-1L protein by thromboxane A2 antagonists enhances cisplatin-induced apoptosis in non-small-cell lung-cancer cell lines. J Cancer Res Clin Oncol 125:389–394

    PubMed  CAS  Google Scholar 

  • Fukumoto K, Yano Y, Virgona N, Hagiwara H, Sato H, Senba H, Suzuki K, Asano R, Yamada K, Yano T (2005) Peroxisome proliferator-activated receptor delta as a molecular target to regulate lung cancer cell growth. FEBS Lett 579:3829–3836

    PubMed  CAS  Google Scholar 

  • Fulzele SV, Chatterjee A, Shaik MS, Jackson T, Singh M (2006) Inhalation delivery and anti-tumor activity of celecoxib in human orthotopic non-small cell lung cancer xenograft model. Pharm Res 23:2094–2106

    PubMed  CAS  Google Scholar 

  • Gradilone A, Silvestri I, Scarpa S, Morrone S, Gandini O, Pulcinelli FM, Gianni W, Frati L, Agliano AM, Gazzaniga P (2007) Failure of apoptosis and activation on NFkappaB by celecoxib and aspirin in lung cancer cell lines. Oncol Rep 17:823–828

    PubMed  CAS  Google Scholar 

  • Han S, Roman J (2006) COX-2 inhibitors suppress lung cancer cell growth by inducing p21 via COX-2 independent signals. Lung Cancer 51:283–296

    Google Scholar 

  • Harris RE, Beebe-Donk J, Alshafie GA (2007) Reduced risk of human lung cancer by selective cyclooxygenase 2 (COX-2) blockade: results of a case control study. Int J Biol Sci 3:328–334

    PubMed  CAS  Google Scholar 

  • Harris RE, Beebe-Donk J, Schuller HM (2002) Chemoprevention of lung cancer by non-steroidal anti-inflammatory drugs among cigarette smokers. Oncol Rep 9:693–695

    PubMed  CAS  Google Scholar 

  • Haurand M, Ullrich V (1985) Isolation and characterization of thromboxane synthase from human platelets as a cytochrome P-450 enzyme. J Biol Chem 260:15059–15067

    PubMed  CAS  Google Scholar 

  • Haynes A, Shaik MS, Chatterjee A, Singh M (2003) Evaluation of an aerosolized selective COX-2 inhibitor as a potentiator of doxorubicin in a non-small-cell lung cancer cell line. Pharm Res 20:1485–1495

    PubMed  CAS  Google Scholar 

  • Hemminki K, Lonnstedt I, Vaittinen P, Lichtenstein P (2001) Estimation of genetic and environmental components in colorectal and lung cancer and melanoma. Genet Epidemiol 20:107–116

    PubMed  CAS  Google Scholar 

  • Herschman HR (1996) Prostaglandin synthase 2. Biochim Biophys Acta 1299:125–140

    PubMed  Google Scholar 

  • Hida T, Kozaki K, Ito H, Miyaishi O, Tatematsu Y, Suzuki T, Matsuo K, Sugiura T, Ogawa M, Takahashi T (2002) Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents. Clin Cancer Res 8:2443–2447

    PubMed  CAS  Google Scholar 

  • Hida T, Kozaki K, Muramatsu H, Masuda A, Shimizu S, Mitsudomi T, Sugiura T, Ogawa M, Takahashi T (2000) Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines. Clin Cancer Res 6:2006–2011

    PubMed  CAS  Google Scholar 

  • Hohla F, Schally AV, Kanashiro CA, Buchholz S, Baker B, Kannadka C, Moder A, Aigner E, Datz C, Halmos G (2007) Growth inhibition of non-small-cell lung carcinoma by BN/GRP antagonist is linked with suppression of K-Ras, COX-2, and pAkt. Proc Natl Acad Sci USA 104:18671–18676

    PubMed  CAS  Google Scholar 

  • Hubbard WC, Alley MC, Gray GN, Green KC, McLemore TL, Boyd MR (1989) Evidence for prostanoid biosynthesis as a biochemical feature of certain subclasses of non-small cell carcinomas of the lung as determined in established cell lines derived from human lung tumors. Cancer Res 49:826–832

    PubMed  CAS  Google Scholar 

  • Hubbard WC, Alley MC, McLemore TL, Boyd MR (1988) Evidence for thromboxane biosynthesis in established cell lines derived from human lung adenocarcinomas. Cancer Res 48:2674–2677

    PubMed  CAS  Google Scholar 

  • Huerta S, Goulet EJ, Huerta-Yepez S, Livingston EH (2007) Screening and detection of apoptosis. J Surg Res 139:143–156

    PubMed  CAS  Google Scholar 

  • Jang MH, Shin MC, Lim S, Han SM, Park HJ, Shin I, Lee JS, Kim KA, Kim EH, Kim CJ (2003) Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299. J Pharmacol Sci 91:95–104

    PubMed  CAS  Google Scholar 

  • Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ (2003) Cancer statistics,2003. CA Cancer J Clin 53:5–26

    PubMed  Google Scholar 

  • Jin Z, Gao F, Flagg T, Deng X (2004) Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation. J Biol Chem 279:40209–40219

    PubMed  CAS  Google Scholar 

  • Joseph B, Ekedahl J, Sirzen F, Lewensohn R, Zhivotovsky B (1999) Differences in expression of pro-caspases in small cell and non-small cell lung carcinoma. Biochem Biophys Res Commun 262:381–387

    PubMed  CAS  Google Scholar 

  • Kaliberov SA, Buchsbaum DJ, Gillespie GY, Curiel DT, Arafat WO, Carpenter M, Stackhouse MA (2002) Adenovirus-mediated transfer of BAX driven by the vascular endothelial growth factor promoter induces apoptosis in lung cancer cells. Mol Ther 6:190–198

    PubMed  CAS  Google Scholar 

  • Karin M, Lin A (2002) NF-kappaB at the crossroads of life and death. Nat Immunol 3:221–227

    PubMed  CAS  Google Scholar 

  • Keith RL, Miller YE, Hudish TM, Girod CE, Sotto-Santiago S, Franklin WA, Nemenoff RA, March TH, Nana-Sinkam SP, Geraci MW (2004) Pulmonary prostacyclin synthase overexpression chemoprevents tobacco smoke lung carcinogenesis in mice. Cancer Res 64:5897–5904

    PubMed  CAS  Google Scholar 

  • Kreutzer M, Fauti T, Kaddatz K, Seifart C, Neubauer A, Schweer H, Kömhoff M, Müller-Brüsselbach S, Müller R. (2007) Specific components of prostanoid-signaling pathways are present in non-small cell lung cancer cells. Oncol Rep 18:497–501

    PubMed  CAS  Google Scholar 

  • Krysan K, Merchant FH, Zhu L, Dohadwala M, Luo J, Lin Y, Heuze-Vourc’h N, Pold M, Seligson D, Chia D, Goodglick L, Wang H, Strieter R, Sharma S, Dubinett S (2004) COX-2-dependent stabilization of survivin in non-small cell lung cancer. Faseb J18:206–208

    PubMed  CAS  Google Scholar 

  • Krysan K, Reckamp KL, Sharma S, Dubinett SM (2006) The potential and rationale for COX-2 inhibitors in lung cancer. Anticancer Agents Med Chem 6:209–220

    PubMed  CAS  Google Scholar 

  • Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR (1991) TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 266:12866–12872

    PubMed  CAS  Google Scholar 

  • Kujubu DA, Herschman HR (1992) Dexamethasone inhibits mitogen induction of the TIS10 prostaglandin synthase/cyclooxygenase gene. J Biol Chem 267:7991–7994

    PubMed  CAS  Google Scholar 

  • Lee HY, Suh YA, Kosmeder JW, Pezzuto JM, Hong WK, Kurie JM (2004) Deguelin-induced inhibition of cyclooxygenase-2 expression in human bronchial epithelial cells. Clin Cancer Res 10:1074–1079

    PubMed  CAS  Google Scholar 

  • Li M, Lee TW, Mok TS, Warner TD, Yim AP, Chen GG (2005) Activation of peroxisome proliferator-activated receptor-gamma by troglitazone (TGZ) inhibits human lung cell growth. J Cell Biochem 96:760–774

    PubMed  CAS  Google Scholar 

  • Liao Z, Mason KA, Milas L (2007) Cyclo-oxygenase-2 and its inhibition in cancer: is there a role? Drugs 67:821–845

    Google Scholar 

  • Lim ES, Rhee YH, Park MK, Shim BS, Ahn KS, Kang H, Yoo HS, Kim SH (2007) DMNQ S-64 induces apoptosis via caspase activation and cyclooxygenase-2 inhibition in human nonsmall lung cancer cells. Ann N Y Acad Sci 1095:7–18

    PubMed  CAS  Google Scholar 

  • Liou JY, Aleksic N, Chen SF, Han TJ, Shyue SK, Wu KK (2005) Mitochondrial localization of cyclooxygenase-2 and calcium-independent phospholipase A2 in human cancer cells: implication in apoptosis resistance. Exp Cell Res 306:75–84

    PubMed  CAS  Google Scholar 

  • Liu X, Yue P, Zhou Z, Khuri FR, Sun SY (2004) Death receptor regulation and celecoxib-induced apoptosis in human lung cancer cells. J Natl Cancer Inst 96:1769–1780

    PubMed  CAS  Google Scholar 

  • Losert D, Pratscher B, Soutschek J, Geick A, Vornlocher HP, Muller M, Wacheck V (2007) Bcl-2 downregulation sensitizes nonsmall cell lung cancer cells to cisplatin, but not to docetaxel. Anticancer Drugs 18:755–761

    PubMed  CAS  Google Scholar 

  • Luo JL, Kamata H, Karin M (2005) The anti-death machinery in IKK/NF-kappaB signaling. J Clin Immunol 25:541–550

    Google Scholar 

  • Mathieu A, Remmelink M, D’Haene N, Penant S, Gaussin JF, Van Ginckel R, Darro F, Kiss R, Salmon I (2004) Development of a chemoresistant orthotopic human nonsmall cell lung carcinoma model in nude mice: analyses of tumor heterogenity in relation to the immunohistochemical levels of expression of cyclooxygenase-2, ornithine decarboxylase, lung-related resistance protein, prostaglandin E synthetase, and glutathione-S-transferase-alpha (GST)-alpha, GST-mu, and GST-pi. Cancer 101:1908–1918

    PubMed  CAS  Google Scholar 

  • McLemore TL, Hubbard WC, Litterst CL, Liu MC, Miller S, McMahon NA, Eggleston JC, Boyd MR (1988) Profiles of prostaglandin biosynthesis in normal lung and tumor tissue from lung cancer patients. Cancer Res 48:3140–3147

    PubMed  CAS  Google Scholar 

  • Miyata A, Yokoyama C, Ihara H, Bandoh S, Takeda O, Takahashi E, Tanabe T (1994) Characterization of the human gene (TBXAS1) encoding thromboxane synthase. Eur J Biochem 224:273–279

    PubMed  CAS  Google Scholar 

  • Mortenson MM, Schlieman MG, Virudachalam S, Lara PN, Gandara DG, Davies AM, Bold RJ (2005) Reduction in BCL-2 levels by 26S proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer. Lung Cancer 49:163–170

    PubMed  Google Scholar 

  • Motadi LR, Misso NL, Dlamini Z, Bhoola KD (2007) Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: therapeutic targets. Int Immunopharmacol 7:1934–1947

    PubMed  CAS  Google Scholar 

  • Nana-Sinkam P, Golpon H, Keith RL, Oyer RJ, Sotto-Santiago S, Moore MD, Franklin W, Nemenoff RA, Geraci MW (2004) Prostacyclin in human non-small cell lung cancers. Chest 125:141S

    PubMed  Google Scholar 

  • Nardone PA, Slotman GJ, Vezeridis MP (1988) Ketoconazole: a thromboxane synthetase and 5-lipoxygenase inhibitor with antimetastatic activity in B16-F10 melanoma. J Surg Res 44:425–449

    PubMed  CAS  Google Scholar 

  • Neilan TG, Jassal DS, Scully MF, Chen G, Deflandre C, McAllister H, Kay E, Austin SC, Halpern EF, Harmey JH, Fitzgerald DJ (2006) Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without compromising tumour suppression. Eur Heart J 27:1251–6

    PubMed  CAS  Google Scholar 

  • Nymark P, Wikman H, Hienonen-Kempas T, Anttila S (2008) Molecular and genetic changes in asbestos-related lung cancer. Cancer Lett 265:1–15

    PubMed  CAS  Google Scholar 

  • Ohmura Y, Aoe M, Andou A, Shimizu N (2000) Telomerase activity and Bcl-2 expression in non-small cell lung cancer. Clin Cancer Res 6:2980–2987

    PubMed  CAS  Google Scholar 

  • Papa S, Bubici C, Zazzeroni F, Pham CG, Kuntzen C, Knabb JR, Dean K, Franzoso G (2006) The NF-kappaB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease. Cell Death Differ 13:712–729

    PubMed  CAS  Google Scholar 

  • Park DI, Choi HY, Kam CW, Park C, Choi TH, Lee WH, Choi YH (2004) Wikyungtang inhibits proliferation of A549 human lung cancer cells via inducing apoptosis and suppressing cyclooxygenase-2 activity. Oncol Rep 11:853–856

    PubMed  CAS  Google Scholar 

  • Petkova DK, Clelland C, Ronan J, Pang L, Coulson JM, Lewis S, Knox AJ (2004) Overexpression of cyclooxygenase-2 in non-small cell lung cancer. Respir Med 98:164–172

    PubMed  CAS  Google Scholar 

  • Pyo H, Choy H, Amorino GP, Kim JS, Cao Q, Hercules SK, DuBois RN (2001) A selective cyclooxygenase-2 inhibitor, NS-398, enhances the effect of radiation in vitro and in vivo preferentially on the cells that express cyclooxygenase-2. Clin Cancer Res 7:2998–3005

    PubMed  CAS  Google Scholar 

  • Reckamp KL, Krysan K, Morrow JD, Milne GL, Newman RA, Tucker C, Elashoff RM, Dubinett SM, Figlin RA (2006) A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer. Clin Cancer Res 12:3381–3388

    PubMed  CAS  Google Scholar 

  • Rioux N, Castonguay A (2000) The induction of cyclooxygenase-1 by a tobacco carcinogen in U937 human macrophages is correlated to the activation of NF-kappaB. Carcinogenesis 21:1745–1751

    PubMed  CAS  Google Scholar 

  • Ruosaari S, Nymark P, Aavikko M, Kettunen E, Knuutila S, Hollmen J, Norppa H, Anttila S (2008) Aberrations of chromosome 19 in asbestos-associated lung cancer and in asbestos-induced micronuclei of bronchial epithelial cells in vitro. Carcinogenesis

    Google Scholar 

  • Sarkar FH, Adsule S, Li Y, Padhye S (2007) Back to the future: COX-2 inhibitors for chemoprevention and cancer therapy. Mini Rev Med Chem 7:599–608

    PubMed  CAS  Google Scholar 

  • Schroeder CP, Yang P, Newman RA, Lotan R (2007) Simultaneous inhibition of COX-2 and 5-LOX activities augments growth arrest and death of premalignant and malignant human lung cell lines. J Exp Ther Oncol 6:183–192

    PubMed  CAS  Google Scholar 

  • Schuller HM (2002) Mechanisms of smoking-related lung and pancreatic adenocarcinoma development. Nat Rev Cancer 2:455–463

    PubMed  CAS  Google Scholar 

  • Schuller HM, Tithof PK, Williams M, Plummer H, 3rd (1999) The tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone is a beta-adrenergic agonist and stimulates DNA synthesis in lung adenocarcinoma via beta-adrenergic receptor-mediated release of arachidonic acid. Cancer Res 59:4510–4515

    PubMed  CAS  Google Scholar 

  • Seiler N, Raul F (2005) Polyamines and apoptosis. J Cell Mol Med 9:623–642

    PubMed  CAS  Google Scholar 

  • Shaik MS, Chatterjee A, Jackson T, Singh M (2006) Enhancement of antitumor activity of docetaxel by celecoxib in lung tumors. Int J Cancer 118:396–404

    PubMed  CAS  Google Scholar 

  • Shaik MS, Chatterjee A, Singh M (2004) Effect of a selective cyclooxygenase-2 inhibitor, nimesulide, on the growth of lung tumors and their expression of cyclooxygenase-2 and peroxisome proliferator- activated receptor-gamma. Clin Cancer Res 10:1521–1529

    PubMed  CAS  Google Scholar 

  • Sharma S, Stolina M, Yang SC, Baratelli F, Lin JF, Atianzar K, Luo J, Zhu L, Lin Y, Huang M, Dohadwala M, Batra RK, Dubinett SM (2003) Tumor cyclooxygenase 2-dependent suppression of dendritic cell function. Clin Cancer Res 9:961–968

    PubMed  CAS  Google Scholar 

  • Shen RF, Tai HH (1986a) Immunoaffinity purification and characterization of thromboxane synthase from porcine lung. J Biol Chem 261:11592–11599

    Google Scholar 

  • Shen RF, Tai HH (1986b) Monoclonal antibodies to thromboxane synthase from porcine lung. Production and application to development of a tandem immunoradiometric assay. J Biol Chem 261:11585–11591

    Google Scholar 

  • Shin YK, Park JS, Kim HS, Jun HJ, Kim GE, Suh CO, Yun YS, Pyo H (2005) Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels. Cancer Res 65:9501–9509

    PubMed  CAS  Google Scholar 

  • Shishodia S, Koul D, Aggarwal BB (2004) Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates TNF-induced NF-kappa B activation through inhibition of activation of I kappa B alpha kinase and Akt in human non-small cell lung carcinoma: correlation with suppression of COX-2 synthesis. J Immunol 173:2011–2022

    PubMed  CAS  Google Scholar 

  • Shivapurkar N, Reddy J, Chaudhary PM, Gazdar AF (2003) Apoptosis and lung cancer: a review. J Cell Biochem 88:885–898

    PubMed  CAS  Google Scholar 

  • Shivapurkar N, Toyooka S, Eby MT, Huang CX, Sathyanarayana UG, Cunningham HT, Reddy JL, Brambilla E, Takahashi T, Minna JD, Chaudhary PM, Gazdar AF (2002) Differential inactivation of caspase-8 in lung cancers. Cancer Biol Ther 1:65–69

    PubMed  CAS  Google Scholar 

  • Soini Y, Paakko P, Lehto VP (1998) Histopathological evaluation of apoptosis in cancer. Am J Pathol 153:1041–1053

    PubMed  CAS  Google Scholar 

  • Stathopoulos GT, Sherrill TP, Cheng DS, Scoggins RM, Han W, Polosukhin VV, Connelly L, Yull FE, Fingleton B, Blackwell TS (2007) Epithelial NF-kappaB activation promotes urethane-induced lung carcinogenesis. Proc Natl Acad Sci USA 104:18514–18519

    PubMed  CAS  Google Scholar 

  • Stearman RS, Grady MC, Nana-Sinkam P, Varella-Garcia M, Geraci MW (2007) Genetic and epigenetic regulation of the human prostacyclin synthase promoter in lung cancer cell lines. Mol Cancer Res 5:295–308

    PubMed  CAS  Google Scholar 

  • Steele VE, Holmes CA, Hawk ET, Kopelovich L, Lubet RA, Crowell JA, Sigman CC, Kelloff GJ (1999) Lipoxygenase inhibitors as potential cancer chemopreventives. Cancer Epidemiol Biomarkers Prev 8:467–483

    PubMed  CAS  Google Scholar 

  • Toussaint C, Albin N, Massaad L, Grunenwald D, Parise O, Jr., Morizet J, Gouyette A, Chabot GG (1993) Main drug- and carcinogen-metabolizing enzyme systems in human non-small cell lung cancer and peritumoral tissues. Cancer Res 53:4608–4612

    PubMed  CAS  Google Scholar 

  • Tsubouchi Y, Mukai S, Kawahito Y, Yamada R, Kohno M, Inoue K, Sano H (2000) Meloxicam inhibits the growth of non-small cell lung cancer. Anticancer Res 20:2867–2872

    PubMed  CAS  Google Scholar 

  • Tsujii M, Kawano S, DuBois RN (1997) Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci USA 94:3336–3340

    PubMed  CAS  Google Scholar 

  • Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705–716

    PubMed  CAS  Google Scholar 

  • Tsurutani J, Castillo SS, Brognard J, Granville CA, Zhang C, Gills JJ, Sayyah J, Dennis PA (2005) Tobacco components stimulate Akt-dependent proliferation and NFkappaB-dependent survival in lung cancer cells. Carcinogenesis 26:1182–1195

    PubMed  CAS  Google Scholar 

  • Vegeler RC, Yip-Schneider MT, Ralstin M, Wu H, Crooks PA, Neelakantan S, Nakshatri H, Sweeney CJ, Schmidt CM (2007) Effect of celecoxib and novel agent LC-1 in a hamster model of lung cancer. J Surg Res 143:169–176

    PubMed  CAS  Google Scholar 

  • Vineis P, Alavanja M, Buffler P, Fontham E, Franceschi S, Gao YT, Gupta PC, Hackshaw A, Matos E, Samet J, Sitas F, Smith J, Stayner L, Straif K, Thun MJ, Wichmann HE, Wu AH, Zaridze D, Peto R, Doll R (2004) Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 96:99–106

    PubMed  CAS  Google Scholar 

  • Voortman J, Checinska A, Giaccone G, Rodriguez JA, Kruyt FA (2007a) Bortezomib, but not cisplatin, induces mitochondria-dependent apoptosis accompanied by up-regulation of noxa in the non-small cell lung cancer cell line NCI-H460. Mol Cancer Ther 6:1046–1053

    Google Scholar 

  • Voortman J, Resende TP, Abou El Hassan MA, Giaccone G, Kruyt FA (2007b) TRAIL therapy in non-small cell lung cancer cells: sensitization to death receptor-mediated apoptosis by proteasome inhibitor bortezomib. Mol Cancer Ther 6:2103–2112

    Google Scholar 

  • Wang L, Chanvorachote P, Toledo D, Stehlik C, Mercer RR, Castranova V, Rojanasakul Y (2008) Peroxide is a key mediator of Bcl-2 down-regulation and apoptosis induction by cisplatin in human lung cancer cells. Mol Pharmacol 73:119–127

    PubMed  CAS  Google Scholar 

  • Wei J, Yan W, Li X, Chang WC, Tai HH (2007) Activation of thromboxane receptor alpha induces expression of cyclooxygenase-2 through multiple signaling pathways in A549 human lung adenocarcinoma cells. Biochem Pharmacol 74:787–800

    PubMed  CAS  Google Scholar 

  • Wennogle LP, Liang H, Quintavalla JC, Bowen BR, Wasvary J, Miller DB, Allentoff A, Boyer W, Kelly M, Marshall P (1995) Comparison of recombinant cyclooxygenase-2 to native isoforms: aspirin labeling of the active site. FEBS Lett 371:315–320

    PubMed  CAS  Google Scholar 

  • West KA, Brognard J, Clark AS, Linnoila IR, Yang X, Swain SM, Harris C, Belinsky S, Dennis PA (2003) Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. J Clin Invest 111:81–90

    PubMed  CAS  Google Scholar 

  • Williams CS, Mann M, DuBois RN (1999) The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18:7908–7916

    PubMed  CAS  Google Scholar 

  • Wilton T (2004) Cyclooxygenase-2 inhibitors: do they have a role in emergency department prescribing? Emerg Med Australas 16:65–73

    Google Scholar 

  • Wu YJ, Muldoon LL, Neuwelt EA (2005) The chemoprotective agent N-acetylcysteine blocks cisplatin-induced apoptosis through caspase signaling pathway. J Pharmacol Exp Ther 312:424–431

    PubMed  CAS  Google Scholar 

  • Yamamoto T, Nozaki-Taguchi N (1996) Analysis of the effects of cyclooxygenase (COX)-1 and COX-2 in spinal nociceptive transmission using indomethacin, a non-selective COX inhibitor, and NS-398, a COX-2 selective inhibitor. Brain Res 739:104–110

    PubMed  CAS  Google Scholar 

  • Yang X, Zheng F, Xing H, Gao Q, Wei W, Lu Y, Wang S, Zhou J, Hu W, Ma D (2004) Resistance to chemotherapy-induced apoptosis via decreased caspase-3 activity and overexpression of antiapoptotic proteins in ovarian cancer. J Cancer Res Clin Oncol 130:423–428

    PubMed  CAS  Google Scholar 

  • Yao R, Rioux N, Castonguay A, You M (2000) Inhibition of COX-2 and induction of apoptosis: two determinants of nonsteroidal anti-inflammatory drugs’ chemopreventive efficacies in mouse lung tumorigenesis. Exp Lung Res 26:731–742

    PubMed  Google Scholar 

  • Yoshimatsu K, Altorki NK, Golijanin D, Zhang F, Jakobsson PJ, Dannenberg AJ, Subbaramaiah K (2001) Inducible prostaglandin E synthase is overexpressed in non-small cell lung cancer. Clin Cancer Res 7:2669–2674

    PubMed  CAS  Google Scholar 

  • Zhang D, Jin X, Wang F, Wang S, Deng C, Gao Z, Guo C (2007) Combined prognostic value of both RelA and IkappaB-alpha expression in human non-small cell lung cancer. Ann Surg Oncol 14:3581–3592

    PubMed  Google Scholar 

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  1. Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong

    Kin Chung Leung & George G. Chen

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  1. Department of Surgery Shatin, Chinese University of Hong Kong Prince of Wales Hospital, Shatin, New Territories, Hong Kong/PR China

    George G. Chen Dr  & Paul B.S. Lai Dr  & 

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Leung, K.C., Chen, G.G. (2009). Cyclooxygenase 2 and its Metabolites: Implications for Lung Cancer Therapy. In: Chen, G.G., Lai, P.B. (eds) Apoptosis in Carcinogenesis and Chemotherapy. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9597-9_11

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