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Antiproliferative Effects of Celecoxib in Hep-2 Cells through Telomerase Inhibition and Induction of Apoptosis

  • Zhao, Yong-Qiang (Department of Otolaryngology & Head and Neck Surgery, the Second Hospital of Shandong University) ;
  • Feng, Hui-Wei (Department of Otolaryngology & Head and Neck Surgery, the Second Hospital of Shandong University) ;
  • Jia, Tao (Department of Otolaryngology & Head and Neck Surgery, the Second Hospital of Shandong University) ;
  • Chen, Xue-Mei (Department of Otolaryngology & Head and Neck Surgery, the Second Hospital of Shandong University) ;
  • Zhang, Hui (Department of Otolaryngology & Head and Neck Surgery, the Second Hospital of Shandong University) ;
  • Xu, An-Ting (Department of Otolaryngology & Head and Neck Surgery, the Second Hospital of Shandong University) ;
  • Zhang, Hai-Ling (Department of Otolaryngology & Head and Neck Surgery, the Second Hospital of Shandong University) ;
  • Fan, Xian-Liang (Department of Otolaryngology & Head and Neck Surgery, the Second Hospital of Shandong University)
  • Published : 2014.06.30

Abstract

Background: To investigate the effect of celecoxib on telomerase activity and apoptosis in a human laryngeal squamous carcinoma cell line (Hep-2 cells). Materials and Methods: The growth inhibition rate of Hep-2 cells in vitro was measured by MTT assay, and apoptosis by TUNEL assay and flow cytometry (FCM). The TRAP-ELISA method was used to determine telomerase activity in Hep-2 cells. The mRNA expression of human telomerase RNA component(hTR), human telomerase reverse transcriptase (hTERT) and human telomerase-associated protein(hTEP1) was determined by RT-PCR assay. Expression of Bax and Bcl-2 proteins was assessed by Western blotting. Results: Celecoxib can inhibit proliferation and induce apoptosis in a dose- and time-dependent manner, repress telomerase activity, decrease hTERT mRNA and Bcl-2 protein expression and increase Bax protein expression, PGE2 had no effect on telomerase. Conclusions: Celecoxib had the antiproliferative and pro-apoptotic effect in Hep-2 cells. Apoptosis was accompanied by a decrease in telomerase activity which was directly correlated with hTERT mRNA and up-regulation of Bax/Bcl-2. Bcl-2 may thus play an important role in telomerase activity as well as apoptosis.

References

  1. Scorrano L, Oakes SA, Opferman JT, et al (2003). BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science, 300, 135-9. https://doi.org/10.1126/science.1081208
  2. Rahmati YM, Ghareghomi S, Haddadchi G, et al (2013). Diosgenin inhibits hTERT gene expression in the A549 lung cancer cell line. Asian Pac J Cancer Prev, 14, 6945-8. https://doi.org/10.7314/APJCP.2013.14.11.6945
  3. Ramer R, Walther U, Borchert P, et al (2013). Induction but not inhibition of COX-2 confers human lung cancer cell apoptosis by celecoxib. J Lipid Res, 54, 3116-29. https://doi.org/10.1194/jlr.M042283
  4. Sato M, Shin K, Lee JI, et al (2012). Human telomerase reverse transcriptase and glucose-regulated protein 78 increase the life span of articular chondrocytes and their repair potential. BMC Musculoskel Dis, 13, 51. https://doi.org/10.1186/1471-2474-13-51
  5. Takakura M, Kyo S, Inoue M, et al (2005). Function of AP-1 in transcription of the telomerase reverse transcriptase gene (TERT) in human and mouse cells. Mol Cell Biol, 25, 8037-43. https://doi.org/10.1128/MCB.25.18.8037-8043.2005
  6. Wang YJ, Niu XP, Yang L, et al (2013). Effects of celecoxib on cycle kinetics of gastric cancer cells and protein expression of cytochrome c and caspase-9. Asian Pac J Cancer Prev, 14, 2343-7. https://doi.org/10.7314/APJCP.2013.14.4.2343
  7. Liu WJ, Jiang JF, Xiao D, et al (2002). Down-regulation of telomerase activity via protein phosphatase 2A activation in salvicine-induced human leukemia HL-60 cell apoptosis. Biochem Pharmacol, 64, 1677-87. https://doi.org/10.1016/S0006-2952(02)01424-7
  8. Ji Z, Ye W, Liu G, et al (2002). 23-Hydroxybetulinic acidmediated apoptosis is accompanied by decreases in bcl-2 expression and telomerase activity in HL-60 Cells. Life Sci, 72, 1-9. https://doi.org/10.1016/S0024-3205(02)02176-8
  9. Johnstone RW, Ruefli AA, Lowe SW, et al (2002). Apoptosis: a link between cancer genetics and chemotherapy. Cell, 108, 153-64. https://doi.org/10.1016/S0092-8674(02)00625-6
  10. Klsmet K, Akay MT, Abbasolu O, et al (2004). Celecoxib: a potent cyclooxygenase-2 inhibitor in cancer prevention. Cancer Detect Prev, 28, 127-42. https://doi.org/10.1016/j.cdp.2003.12.005
  11. Mandal M, Kumar R (1997). Bcl-2 modulates telomerase activity. J Biol Chem, 272, 14183-7. https://doi.org/10.1074/jbc.272.22.14183
  12. Murnane JP (2010). Telomere loss as a mechanism for chromosome instability in human cancer. Cancer Res, 70, 4255-9. https://doi.org/10.1158/0008-5472.CAN-09-4357
  13. Ninomiya I, Nagai N, Oyama K, et al (2012). Antitumor and anti-metastatic effects of cyclooxygenase-2 inhibition by celecoxib on human colorectal carcinoma xenografts in nude mouse rectum. Oncol Rep, 28, 777-84. https://doi.org/10.3892/or.2012.1885
  14. Pang RP, Zhou JG, Zeng ZR, et al (2007). Celecoxib induces apoptosis in COX-2 deficient human gastric cancer cells through Akt/GSK3 beta/NAG-1 pathway. Cancer Lett, 251, 268-77. https://doi.org/10.1016/j.canlet.2006.11.032
  15. Perez-Ruiz E, Cazorla O, Redondo M, et al (2012). Immunohistochemical expression of cyclooxygenase-2 in patients with advanced cancer of the larynx who have undergone induction chemotherapy with the intention of preserving phonation. Clin Transl Oncol, 14, 682-8. https://doi.org/10.1007/s12094-012-0859-2
  16. Pruegsanusak K, Peeravut S, Leelamanit V, et al (2012). Survival and prognostic factors of different sites of head and neck cancer: an analysis from Thailand. Asian Pac J Cancer Prev, 13, 885-90. https://doi.org/10.7314/APJCP.2012.13.3.885
  17. Fu WM, Begley JG, Killen MW, et al (1999). Anti-apoptotic role of telomerase in pheochromocytoma cells. J Biol Chem, 274, 7264-71. https://doi.org/10.1074/jbc.274.11.7264
  18. Bocca C, Bozzo F, Cannito S, et al (2012). Celecoxib inactivates epithelial-mesenchymal transition stimulated by hypoxia and/or epidermal growth factor in colon cancer cells. J Mol Carcinogen, 51, 783-5. https://doi.org/10.1002/mc.20846
  19. Du LB, Mao WM, Chen WQ, et al (2012). Incidence and mortality of larynx cancer in China during 2003-2007. Chinese J Epidemiol, 33, 395-8.
  20. Forastiere A, Zhang Q, Weber RS, et al (2013). Long-Term Results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol, 31, 845-52. https://doi.org/10.1200/JCO.2012.43.6097
  21. Gino M, Rosario M-R, Giuseppe CG, et al (2006). Current opinion in diagnosis and treatment of laryngeal carcinoma. Cancer Treat Rev, 32, 504-15. https://doi.org/10.1016/j.ctrv.2006.07.002
  22. Guo W, Li GJ, Xu HB, et al (2012). In vitro biological characterization of DCUN1D5 in DNA damage response. Asian Pac J Cancer Pre, 13, 4157-62. https://doi.org/10.7314/APJCP.2012.13.8.4157
  23. Harizi H, Juzan M, Pitard V, et al (2002). Cyclooxygenase-2-issued prostaglandin E2 enhances the production of endogenous IL-10, which down-regulates dendritic cellfunctions. J lmmunology, 168, 2255-63.
  24. Jemal A, Siegel R, Xu J, et al (2010). Cancer Statistics, 2010. Ca-cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
  25. Jeon YW, Suh YJ (2013). Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells. Oncol Rep, 29, 819-25. https://doi.org/10.3892/or.2012.2158
  26. Jeong SY, Seol DW (2008). The role of mitochondria in apoptosis. BMB Rep, 41, 11-22. https://doi.org/10.5483/BMBRep.2008.41.1.011
  27. Armstrong RC, Aja T, Xiang J, et al (1996). Fas-induced activation of the cell death-related protease cpp32 is inhibited by bcl-2 and by ICE family protease inhibitors. J Biol Chem, 271, 16850-5. https://doi.org/10.1074/jbc.271.28.16850

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