Journal of the Korean Association of Oral and Maxillofacial Surgeons

The Korean Association of Oral and Maxillofacial Surgeons (대한구강악안면외과학회)
권호 표지
DOI QR코드

DOI QR Code

The influence of p53 mutation status on the anti-cancer effect of cisplatin in oral squamous cell carcinoma cell lines

  • Jo, Deuk-Won (Department of Prosthodontics, Section of Dentistry, Seoul National University Bundang Hospital) ;
  • Kim, Young-Kyun (Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital) ;
  • Yun, Pil-Young (Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital)
  • Received : 2016.09.01
  • Accepted : 2016.10.07
  • Published : 2016.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: The purpose of this study was to evaluate the anti-cancer activity of cisplatin by studying its effects on cell viability and identifying the mechanisms underlying the induction of cell cycle arrest and apoptosis on oral squamous cell carcinoma (OSCC) cell lines with varying p53 mutation status. Materials and Methods: Three OSCC cell lines, YD-8 (p53 point mutation), YD-9 (p53 wild type), and YD-38 (p53 deletion) were used. To determine the cytotoxic effect of cisplatin, MTS assay was performed. The cell cycle alteration and apoptosis were analyzed using flow cytometry. Western blot analysis was used to detect the expression of cell cycle alteration- or apoptosis-related proteins as well as p53. Results: Cisplatin showed a time- and dose-dependent anti-proliferative effect in all cell lines. Cisplatin induced G2/M cell accumulation in the three cell lines after treatment with 0.5 and $1.0{\mu}g/mL$ of cisplatin for 48 hours. The proportion of annexin V-FITC-stained cells increased following treatment with cisplatin. The apoptotic proportion was lower in the YD-38 cell line than in the YD-9 or YD-8 cell lines. Also, immunoblotting analysis indicated that p53 and p21 were detected only in YD-8 and YD-9 cell lines after cisplatin treatment. Conclusion: In this study, cisplatin showed anti-cancer effects via G2/M phase arrest and apoptosis, with some difference among OSCC cell lines. The mutation status of p53 might have influenced the difference observed among cell lines. Further studies on p53 mutation status are needed to understand the biological behavior and characteristics of OSCCs and to establish appropriate treatment.

Keywords

References

  1. Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol 2001;2:533-43. https://doi.org/10.1016/S1470-2045(01)00486-7
  2. Eastman A. The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes. Pharmacol Ther 1987;34:155-66. https://doi.org/10.1016/0163-7258(87)90009-X
  3. Rossi A, Maione P, Gridelli C. Safety profile of platinum-based chemotherapy in the treatment of advanced non-small cell lung cancer in elderly patients. Expert Opin Drug Saf 2005;4:1051-67. https://doi.org/10.1517/14740338.4.6.1051
  4. Chen XX, Lai MD, Zhang YL, Huang Q. Less cytotoxicity to combination therapy of 5-fluorouracil and cisplatin than 5-fluorouracil alone in human colon cancer cell lines. World J Gastroenterol 2002;8:841-6. https://doi.org/10.3748/wjg.v8.i5.841
  5. Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, et al. Molecular mechanisms of cisplatin resistance. Oncogene 2012;31:1869-83. https://doi.org/10.1038/onc.2011.384
  6. Jiang T, Zhou C, Gu J, Liu Y, Zhao L, Li W, et al. Enhanced therapeutic effect of cisplatin on the prostate cancer in tumor-bearing mice by transfecting the attenuated Salmonella carrying a plasmid co-expressing p53 gene and mdm2 siRNA. Cancer Lett 2013;337:133-42. https://doi.org/10.1016/j.canlet.2013.05.028
  7. Mantoni TS, Reid G, Garrett MD. Androgen receptor activity is inhibited in response to genotoxic agents in a p53-independent manner. Oncogene 2006;25:3139-49. https://doi.org/10.1038/sj.onc.1209347
  8. Lee EJ, Kim J, Lee SA, Kim EJ, Chun YC, Ryu MH, et al. Characterization of newly established oral cancer cell lines derived from six squamous cell carcinoma and two mucoepidermoid carcinoma cells. Exp Mol Med 2005;37:379-90. https://doi.org/10.1038/emm.2005.48
  9. Booher RN, Holman PS, Fattaey A. Human Myt1 is a cell cycleregulated kinase that inhibits Cdc2 but not Cdk2 activity. J Biol Chem 1997;272:22300-6. https://doi.org/10.1074/jbc.272.35.22300
  10. Liu F, Stanton JJ, Wu Z, Piwnica-Worms H. The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex. Mol Cell Biol 1997;17:571-83. https://doi.org/10.1128/MCB.17.2.571
  11. Parker LL, Piwnica-Worms H. Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science 1992;257:1955-7. https://doi.org/10.1126/science.1384126
  12. Chang BD, Xuan Y, Broude EV, Zhu H, Schott B, Fang J, et al. Role of p53 and p21waf1/cip1 in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs. Oncogene 1999;18:4808-18. https://doi.org/10.1038/sj.onc.1203078
  13. Dhar S, Kolishetti N, Lippard SJ, Farokhzad OC. Targeted delivery of a cisplatin prodrug for safer and more effective prostate cancer therapy in vivo. Proc Natl Acad Sci U S A 2011;108:1850-5. https://doi.org/10.1073/pnas.1011379108
  14. Xu X, Xie K, Zhang XQ, Pridgen EM, Park GY, Cui DS, et al. Enhancing tumor cell response to chemotherapy through nanoparticlemediated codelivery of siRNA and cisplatin prodrug. Proc Natl Acad Sci U S A 2013;110:18638-43. https://doi.org/10.1073/pnas.1303958110
  15. Weinstein JN, Myers TG, O'Connor PM, Friend SH, Fornace AJ Jr, Kohn KW, et al. An information-intensive approach to the molecular pharmacology of cancer. Science 1997;275:343-9. https://doi.org/10.1126/science.275.5298.343
  16. Kovach JS, Hartmann A, Blaszyk H, Cunningham J, Schaid D, Sommer SS. Mutation detection by highly sensitive methods indicates that p53 gene mutations in breast cancer can have important prognostic value. Proc Natl Acad Sci U S A 1996;93:1093-6. https://doi.org/10.1073/pnas.93.3.1093
  17. Wattel E, Preudhomme C, Hecquet B, Vanrumbeke M, Quesnel B, Dervite I, et al. p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood 1994;84:3148-57.
  18. Bradford CR, Zhu S, Poore J, Fisher SG, Beals TF, Thoraval D, et al. p53 mutation as a prognostic marker in advanced laryngeal carcinoma. Department of Veterans Affairs Laryngeal Cancer Cooperative Study Group. Arch Otolaryngol Head Neck Surg 1997;123:605-9. https://doi.org/10.1001/archotol.1997.01900060047008
  19. Bradford CR, Zhu S, Ogawa H, Ogawa T, Ubell M, Narayan A, et al. P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines. Head Neck 2003;25:654-61. https://doi.org/10.1002/hed.10274
  20. Zamble DB, Jacks T, Lippard SJ. p53-Dependent and -independent responses to cisplatin in mouse testicular teratocarcinoma cells. Proc Natl Acad Sci U S A 1998;95:6163-8. https://doi.org/10.1073/pnas.95.11.6163
  21. Wagner AJ, Kokontis JM, Hay N. Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1. Genes Dev 1994;8:2817-30. https://doi.org/10.1101/gad.8.23.2817
  22. Siddik ZH, Mims B, Lozano G, Thai G. Independent pathways of p53 induction by cisplatin and X-rays in a cisplatin-resistant ovarian tumor cell line. Cancer Res 1998;58:698-703.
  23. Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 1990;63:1129-36. https://doi.org/10.1016/0092-8674(90)90409-8
  24. Wong RH, Du CL, Wang JD, Chan CC, Luo JC, Cheng TJ. XRCC1 and CYP2E1 polymorphisms as susceptibility factors of plasma mutant p53 protein and anti-p53 antibody expression in vinyl chloride monomer-exposed polyvinyl chloride workers. Cancer Epidemiol Biomarkers Prev 2002;11:475-82.
  25. Yook JI, Kim J. Expression of p21WAF1/CIP1 is unrelated to p53 tumour suppressor gene status in oral squamous cell carcinomas. Oral Oncol 1998;34:198-203. https://doi.org/10.1016/S1368-8375(97)00091-2

Cited by

  1. In vitro FTIR microspectroscopy analysis of primary oral squamous carcinoma cells treated with cisplatin and 5-fluorouracil: a new spectroscopic approach for studying the drug-cell interaction vol.143, pp.14, 2016, https://doi.org/10.1039/c8an00602d
  2. High expression of TMEM40 contributes to progressive features of tongue squamous cell carcinoma vol.41, pp.1, 2019, https://doi.org/10.3892/or.2018.6788
  3. Upregulation of MDR- and EMT-Related Molecules in Cisplatin-Resistant Human Oral Squamous Cell Carcinoma Cell Lines vol.20, pp.12, 2016, https://doi.org/10.3390/ijms20123034
  4. Role of Smoking-Mediated molecular events in the genesis of oral cancers vol.29, pp.9, 2016, https://doi.org/10.1080/15376516.2019.1646372
  5. Synergistic Cytotoxic Effect of Honey Bee Venom and Cisplatin on Tongue Squamous Cell Carcinoma Cell Line vol.9, pp.2, 2020, https://doi.org/10.3889/oamjms.2021.7672