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Article

Usefulness of selective COX-2 inhibitors as therapeutic agents against canine mammary tumors

  • Authors:
    • Teruyoshi Saito
    • Dai Tamura
    • Ryuji Asano
  • View Affiliations / Copyright

    Affiliations: Laboratory of Veterinary Pharmacology, Nihon University College of Bioresource Sciences, Kanagawa 252-8510, Japan
  • Pages: 1637-1644
    |
    Published online on: February 4, 2014
       https://doi.org/10.3892/or.2014.3010
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Abstract

Cyclooxygenase-2 (COX-2) is a key enzyme for converting arachidonic acids to prostanoids, which are known to be induced during inflammation and cancer initiation. Previously, it has been reported that COX inhibitors, such as aspirin, reduce the incidence of human colorectal cancer; therefore, it is widely believed that COX-2 is a potential therapeutic and chemoprevention target for several types of human cancer. However, whether selective COX-2 inhibitors have antitumor effects against canine mammary tumor cells remains unclear. In the present study, to elucidate the antitumor effect of selective COX-2 inhibitors against canine mammary tumors, we investigated the antitumor effects of meloxicam, etodolac and celecoxib using COX-2-expressing canine mammary tumor (CF33) cells. We analyzed the effects of selective COX-2 inhibitors on COX-2 protein expression levels in CF33 cells. Celecoxib (100 µM) was found to induce downregulation of COX-2 protein expression. We examined the effect of selective COX-2 inhibitors on CF33 cell proliferation. All the selective COX-2 inhibitors suppressed CF33 cell growth. Specifically, etodolac and celecoxib inhibited cell proliferation via a decrease in S-phase cells and an increase in G0/G1 arrest. We examined the apoptotic effect of selective COX-2 inhibitors on CF33 cells. Our data suggested that etodolac and celecoxib induced apoptosis in CF33 cells. In particular, celecoxib led to apoptosis mediated by the activation of the mitochondrial apoptosis pathway, including the upregulation of BAX expression, downregulation of Bcl-2 expression and activation of caspase-3/7. Furthermore, celecoxib increased the percentages of cells in both early apoptosis and late apoptosis. Our results revealed that celecoxib induced apoptosis and cell cycle arrest in CF33 cells. The data suggested that celecoxib is the most viable candidate as a therapeutic agent for the treatment of canine mammary tumors. Furthermore, our findings provide the first indication that COX-2 inhibition can provide a new therapeutic strategy for treating canine mammary tumors.
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1 

Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS and Simmons DL: COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci USA. 99:13926–13931. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Dennis LK, Lynch CF and Torner JC: Epidemiologic association between prostatitis and prostate cancer. Urology. 60:78–83. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Howe LR: Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer. Breast Cancer Res. 9:2102007. View Article : Google Scholar : PubMed/NCBI

5 

Coussens LM and Werb Z: Inflammation and cancer. Nature. 420:860–867. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Liao X, Lochhead P, Nishihara R, et al: Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med. 367:1596–1606. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Holmes MD, Chen WY, Li L, Hertzmark E, Spiegelman D and Hankinson SE: Aspirin intake and survival after breast cancer. J Clin Oncol. 28:1467–1472. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Stratmann N, Failing K, Richter A and Wehrend A: Mammary tumor recurrence in bitches after regional mastectomy. Vet Surg. 37:82–86. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Doré M, Lanthier I and Sirois J: Cyclooxygenase-2 expression in canine mammary tumors. Vet Pathol. 40:207–212. 2003.

10 

Queiroga FL, Alves A, Pires I and Lopes C: Expression of Cox-1 and Cox-2 in canine mammary tumours. J Comp Pathol. 136:177–185. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Klopfleisch R, von Euler H, Sarli G, Pinho SS, Gartner F and Gruber AD: Molecular carcinogenesis of canine mammary tumors: news from an old disease. Vet Pathol. 48:98–116. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Saito T, Tamura D, Nakamura T, et al: 4-methylumbelliferone leads to growth arrest and apoptosis in canine mammary tumor cells. Oncol Rep. 29:335–342. 2013.PubMed/NCBI

13 

Saito T, Dai T and Asano R: The hyaluronan synthesis inhibitor 4-methylumbelliferone exhibits antitumor effects against mesenchymal-like canine mammary tumor cells. Oncol Lett. 5:1068–1074. 2013.

14 

Saito T, Kawana H, Azuma K, Toyoda A, Fujita H, Kitagawa M and Harigaya K: Fragmented hyaluronan is an autocrine chemokinetic motility factor supported by the HAS2-HYAL2/CD44 system on the plasma membrane. Int J Oncol. 39:1311–1320. 2011.PubMed/NCBI

15 

Zhang GS, Liu DS, Dai CW and Li RJ: Antitumor effects of celecoxib on K562 leukemia cells are mediated by cell-cycle arrest, caspase-3 activation, and downregulation of Cox-2 expression and are synergistic with hydroxyurea or imatinib. Am J Hematol. 81:242–255. 2006. View Article : Google Scholar : PubMed/NCBI

16 

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

17 

Chipuk JE and Green DR: How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol. 18:157–164. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES and Wang X: Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 91:479–489. 1997. View Article : Google Scholar : PubMed/NCBI

19 

William WN Jr, Heymach JV, Kim ES and Lippman SM: Molecular targets for cancer chemoprevention. Nat Rev Drug Discov. 8:213–225. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Harris RE: Cyclooxygenase-2 (COX-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology. 17:55–67. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Dannenberg AJ and Subbaramaiah K: Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cell. 4:431–436. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Doré M: Cyclooxygenase-2 expression in animal cancers. Vet Pathol. 48:254–265. 2011.

23 

Dias Pereira P, Lopes CC, Matos AJ, Santos M, Gärtner F, Medeiros R and Lopes C: COX-2 expression in canine normal and neoplastic mammary gland. J Comp Pathol. 140:247–253. 2009.PubMed/NCBI

24 

Hengartner MO: The biochemistry of apoptosis. Nature. 407:770–776. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Ola MS, Nawaz M and Ahsan H: Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem. 351:41–58. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Igney FH and Krammer PH: Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer. 2:277–288. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Tait SW and Green DR: Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol. 11:621–632. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Liu X, Yue P, Zhou Z, Khuri FR and Sun SY: Death receptor regulation and celecoxib-induced apoptosis in human lung cancer cells. J Natl Cancer Inst. 96:1769–1780. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Jendrossek V, Handrick R and Belka C: Celecoxib activates a novel mitochondrial apoptosis signaling pathway. FASEB J. 17:1547–1549. 2003.PubMed/NCBI

30 

Jendrossek V: Targeting apoptosis pathways by Celecoxib in cancer. Cancer Lett. 332:313–324. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Sheng H, Shao J, Morrow JD, Beauchamp RD and DuBois RN: Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res. 58:362–366. 1998.PubMed/NCBI

32 

Solomon SD, McMurray JJ, Pfeffer MA, et al: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 352:1071–1080. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Fitzgerald GA: Coxibs and cardiovascular disease. N Engl J Med. 351:1709–1711. 2004. View Article : Google Scholar : PubMed/NCBI

34 

Schönthal AH, Chen TC, Hofman FM, Louie SG and Petasis NA: Celecoxib analogs that lack COX-2 inhibitory function: preclinical development of novel anticancer drugs. Expert Opin Investig Drugs. 17:197–208. 2008.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Saito T, Tamura D and Asano R: Usefulness of selective COX-2 inhibitors as therapeutic agents against canine mammary tumors. Oncol Rep 31: 1637-1644, 2014.
APA
Saito, T., Tamura, D., & Asano, R. (2014). Usefulness of selective COX-2 inhibitors as therapeutic agents against canine mammary tumors. Oncology Reports, 31, 1637-1644. https://doi.org/10.3892/or.2014.3010
MLA
Saito, T., Tamura, D., Asano, R."Usefulness of selective COX-2 inhibitors as therapeutic agents against canine mammary tumors". Oncology Reports 31.4 (2014): 1637-1644.
Chicago
Saito, T., Tamura, D., Asano, R."Usefulness of selective COX-2 inhibitors as therapeutic agents against canine mammary tumors". Oncology Reports 31, no. 4 (2014): 1637-1644. https://doi.org/10.3892/or.2014.3010
Copy and paste a formatted citation
x
Spandidos Publications style
Saito T, Tamura D and Asano R: Usefulness of selective COX-2 inhibitors as therapeutic agents against canine mammary tumors. Oncol Rep 31: 1637-1644, 2014.
APA
Saito, T., Tamura, D., & Asano, R. (2014). Usefulness of selective COX-2 inhibitors as therapeutic agents against canine mammary tumors. Oncology Reports, 31, 1637-1644. https://doi.org/10.3892/or.2014.3010
MLA
Saito, T., Tamura, D., Asano, R."Usefulness of selective COX-2 inhibitors as therapeutic agents against canine mammary tumors". Oncology Reports 31.4 (2014): 1637-1644.
Chicago
Saito, T., Tamura, D., Asano, R."Usefulness of selective COX-2 inhibitors as therapeutic agents against canine mammary tumors". Oncology Reports 31, no. 4 (2014): 1637-1644. https://doi.org/10.3892/or.2014.3010
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