Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Celecoxib, a COX-2 Selective Inhibitor, Induces Cell Cycle Arrest at the G2/M Phase in HeLa Cervical Cancer Cells

  • Setiawati, Agustina (Department of Drug Design and Discovery, Faculty of Pharmacy, Universitas Sanata Dharma)
  • Published : 2016.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

Celecoxib, a selective inhibitor of COX-2, showed cytotoxic effects in many cancer cell lines including cervical cancer cells. This study investigated the effect of celecoxib on cell cycle arrest in HeLa cervical cancer cells through p53 expression. In vitro anticancer activity was determined with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method. A double staining method was applied to investigate the mechanism of cell death, cell cycling was analyzed by flow cytometryand immunocytochemistry was employed to stain p53 expression in cells. Celecoxib showed strong cytotoxic effects and induced apoptosis with an $IC_{50}$ value of $40{\mu}M$. It induced cell cycle arrest at G2/M phase by increasing level of p53 expression on HeLa cells.

Keywords

References

  1. Allaj V, Guo C, Nie D (2013). Non-steroid anti-inflammatory drugs, prostaglandins, and cancer. Cell Biosci, 3, 8. https://doi.org/10.1186/2045-3701-3-8
  2. Ang AHW, Ian XYT, Yu JJ, et al (2012). Celecoxib Radiosensitizes the Human Cervical Cancer HeLa Cell Line via a Mechanism Dependent on Reduced Cyclo-oxygenase-2 and Vascular Endothelial Growth Factor C Expression. J Internl Med Res, 40, 56-66.
  3. Audo R, Deschamps V, Hahne M, Combe B, et al (2007). Apoptosis is not the major death mechanism induced by celecoxib on rheumatoid arthritis synovial fibroblasts. Arthritis Res Ther, 9, 128. https://doi.org/10.1186/ar2342
  4. Chen F, Wang W, El-Deiry WS (2010). Current strategies to target p53 in Cancer. Biochemical Pharmacol, 80, 727-30.
  5. Chu T, Chan H, Kuo H, Liu L, et al (2013). Celecoxib suppresses hepatoma stemness and progression by up-regulating PTEN. Oncotarget, 5, 1475-90.
  6. Dasari S, Tchounwou BP (2014). Cisplatin in Cancer therapy: Molecular mechanisms of action. Eur J Pharmacol, 740, 364-78. https://doi.org/10.1016/j.ejphar.2014.07.025
  7. Doll CM, Winter K, Gaffney DK et al (2013). COX-2 Expression and survival in patients with locally advanced cervical cancer treated with chemoradiotherapy and celecoxib: A quantitative immunohistochemical analysis of RTOG C0128. Int J Gynecol Cancer, 23, 176-83. https://doi.org/10.1097/IGC.0b013e3182791efc
  8. Fernandes SM, Syrjanen KJ (2003). Regulation of cell cycles is of key importance in human papillomavirus (HPV)-asociated cervical carcinogenesis. Sao Paulo Med J, 121, 128-32. https://doi.org/10.1590/S1516-31802003000300009
  9. Galluzzi L, Vitale I, Michels J, Brenner C, et al (2014). Systems biology of cisplatin resistance: past, present and future. Cell Death Dis, 5, 1257. https://doi.org/10.1038/cddis.2013.428
  10. Garofalo C, Surmacz E (2006). Leptin and cancer. J Cell Physiol, 207, 12-22. https://doi.org/10.1002/jcp.20472
  11. Grigsby PW, Zighelboim I, Powell MA, et al (2013). In vitro chemoresponse to cisplatin and outcomes in cervical cancer. Gynecol Oncol, 130, 188-91. https://doi.org/10.1016/j.ygyno.2013.04.005
  12. Gupta SC, Sung B, Prasad S, Webb LJ, et al (2013). Cancer drug discovery by repurposing: Teaching new tricks to old dogs. Trends Pharmacol Sci, 34, 508-17. https://doi.org/10.1016/j.tips.2013.06.005
  13. Gurpinar E, Grizzle WE, Piazza G (2013). COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs. Front Oncol, 3, 1-18.
  14. Hsu AL, Ching TT, Wang DS, et al (2000). The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem, 275, 11397-1403. https://doi.org/10.1074/jbc.275.15.11397
  15. Kang KB, Zhu C, Yong SK, et al (2009). Enhanced sensitivity of celecoxib in human glioblastoma cells: Induction of DNA damage leading to p53-dependent G1 cell cycle arrest and autophagy. Molecular Cancer, 8, 66. https://doi.org/10.1186/1476-4598-8-66
  16. Kang MK, Park W, Choi YL, et al (2009). The effect of cyclooxygenase-2 expression on tumor volume response in patients treated with radiotherapy for uterine cervical cancer. J Korean Med Sci, 24, 1170-76. https://doi.org/10.3346/jkms.2009.24.6.1170
  17. Kim HS, Kim T, Kim M, et al (2013). Cyclooxygenase-1 and -2: Molecular Targets for Cervical Neoplasia. J Cancer Prevent, 18. 123-34. https://doi.org/10.15430/JCP.2013.18.2.123
  18. Kim SH, Hwang CI, Juhnn YS, et al (2007). Erratum: GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells. Carcinogenesis, 28, 223-31. https://doi.org/10.1093/carcin/bgl227
  19. Kim SH, Song SH, Kim SG, et al (2004). Celecoxib induces apoptosis in cervical cancer cells independent of cyclooxygenase using NF-kappaB as a possible target. J Cancer Res Clin Oncol, 130, 551-60.
  20. Kim YM, Pyo H (2013). Different Cell Cycle Modulation by Celecoxib at Different Concentrations. Cancer Biother Radiopharm, 28, 138-45. https://doi.org/10.1089/cbr.2012.1264
  21. Kimman M, Norman R, Jan S, et al (2012). The burden of cancer in member countries of the association of southeast asian nations (ASEAN). Asian Pac J Cancer Prev, 13, 411-20. https://doi.org/10.7314/APJCP.2012.13.2.411
  22. Lane DP, Cheok CF, Lain S (2010). p53-based cancer therapy. Cold Spring Harb Perspect Biol, 2, 1222. https://doi.org/10.1101/cshperspect.a001222
  23. Larasati YA, Putri DPP, Utomo RY, et al (2014). Combination of cisplatin and cinnamon essential oil inhibits hela cells proliferation through cell cycle arrest. J App Pharm Sci, 4, 14-9.
  24. Lee YS, Bae SM, Kwak SY, et al (2006). Cell cycle regulatory protein expression profiles by adenovirus p53 infection in human papilloma virus-associated cervical cancer cells. Cancer Res Treat, 38, 168-77. https://doi.org/10.4143/crt.2006.38.3.168
  25. Li T, Kon N, Jiang L, et al (2012).Tumor suppression in the absence of p53-mediated cell cycle arrest, apoptosis, and senescence. Cell, 149, 1269-83. https://doi.org/10.1016/j.cell.2012.04.026
  26. Liu K, Liu PC, Liu R, et al (2015). Dual AO/EB staining to detect apoptosis in osteosarcoma cells compared with flow cytometry. Med Sci Monit Basic Res, 21, 15-20. https://doi.org/10.12659/MSMBR.893327
  27. Nair P, Somasundaram K, Krishna S (2003). Activated notch1 inhibits p53-induced apoptosis and sustains transformation by human papillomavirus type 16 E6 and E7 oncogenes through a activated notch1 inhibits p53-induced apoptosis and sustains transformation by human papillomavirus type 16 E6 and E7. J Virol, 77, 7106-112. https://doi.org/10.1128/JVI.77.12.7106-7112.2003
  28. Pflaum J, Schlosser S, Müller M (2014). p53 family and cellular stress responses in cancer. Frontier Oncol, 285, 1-15.
  29. Pinheiro NA, Villa LL (2001). Low frequency of p53 mutations in cervical carcinomas among Brazilian women. Brazilian J Med Biol Res, 34, 727-33. https://doi.org/10.1590/S0100-879X2001000600005
  30. Torre LA, Bray F, Siegel RL, et al (2015). Global Cancer Statistics, 2012. CA Cancer J Clin, 15, 87-108
  31. Vici P, Mariani L, Pizzuti L, et al (2014). Emerging biological treatments for uterine cervical carcinoma. J Cancer, 5, 86-97. https://doi.org/10.7150/jca.7963
  32. Sahasrabuddhe VV, Parham GP, Mwanahamuntu MH, et al (2013). Cervical cancer prevention in low- and middleincome countries: Feasible, Affordable, Essential. Cancer Prev Res (Phila), 5, 11-17.
  33. Setiawati A, Immanuel H, Utami MT (2016). Typhonium flagelliforme lodd. blume leaf extract inhibits COX-2 expression on WiDr colon cancer cells. Asian Pac J Trop Biomed, 6.
  34. Wang L, Liu LH, Shan BE, et al (2009). Celecoxib promotes apoptosis of breast cancer cell line MDA-MB-231 through down-regulation of the NF-kappa B pathway. Chin J Cancer, 28, 6.
  35. Wang Y, Niu X, 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, 2343-47. https://doi.org/10.7314/APJCP.2013.14.4.2343
  36. Yuliani SH, Anggraeni CD, Sekarjati W, et al (2015). Cytotoxic Activity of Anredera cordifolia Leaf Extract on HeLa Cervical Cancer Cells through p53-Independent Pathway. Asian J Pharm Clin Res, 8, 328-31.
  37. Zweers MC, de Boer TN, van Roon J, et al (2011). Celecoxib: considerations regarding its potential disease-modifying properties in osteoarthritis. Arthritis Res Ther, 13, 239. https://doi.org/10.1186/ar3437

Cited by

  1. with Antiausterity Activities against the PANC-1 Human Pancreatic Cancer Cell Line vol.80, pp.10, 2017, https://doi.org/10.1021/acs.jnatprod.7b00650
  2. : Chiral Resolution, Configurational Assignment, and Cytotoxic Activities against the HeLa Cancer Cell Line vol.80, pp.5, 2017, https://doi.org/10.1021/acs.jnatprod.7b00180
  3. SKA3 promotes cell proliferation and migration in cervical cancer by activating the PI3K/Akt signaling pathway vol.18, pp.1, 2018, https://doi.org/10.1186/s12935-018-0670-4