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Article

5-Aza-2'-deoxycytidine induces cytotoxicity in BGC-823 cells via DNA methyltransferase 1 and 3a independent of p53 status

  • Authors:
    • Juan Liu
    • Yan Zhang
    • Yi-Shan Xie
    • Fu-Liang Wang
    • Li-Jun Zhang
    • Tao Deng
    • He-Sheng Luo
  • View Affiliations / Copyright

    Affiliations: Department of Geriatrics, Renmin Hospital of Wuhan University, Wuchang District, Wuhan 430060, P.R. China, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuchang District, Wuhan 430060, P.R. China, Department of Oncology, Renmin Hospital of Wuhan University, Wuchang District, Wuhan 430060, P.R. China
  • Pages: 545-552
    |
    Published online on: May 29, 2012
       https://doi.org/10.3892/or.2012.1838
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Abstract

The DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR) has therapeutic value for the treatment of cancer. However, the mechanism by which 5-Aza-CdR induces antineoplastic activity is not clear. The efficacy of 5-Aza-CdR on the contribution of gene reactivation by demethylation and enzyme-DNA adduct formation is an important unresolved question. The aim of this study was to explore the mechanism of the effect of 5-Aza-CdR on human gastric cancer growth. Human BGC-823 cells were treated with different concentrations of 5-Aza-CdR for different durations. Cell viability, DNA damage and gene expression were determined. The results showed that 5-Aza-CdR at low concentrations induced inhibition of gastric cancer BGC-823 cell proliferation as well as increased apoptosis caused by DNA damage. For the first time, we demonstrated that 5-Aza-CdR-induced cytotoxicity against BGC-823 cells was predominantly regulated via upregulation of DNA methyltransferase 1, 3a and partially via reactivation of RUNX3, which was independent of p53 status and its ability to activate p21Waf1/Cip1 expression. To our knowledge, this is the first demonstration of p53-independent 5-Aza-CdR action on DNA methyltransferases and demethylation. These results strongly provide the preclinical rationale for the clinical evaluation of 5-Aza-CdR to improve patient outcome in gastric cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Liu J, Zhang Y, Xie Y, Wang F, Zhang L, Deng T and Luo H: 5-Aza-2'-deoxycytidine induces cytotoxicity in BGC-823 cells via DNA methyltransferase 1 and 3a independent of p53 status. Oncol Rep 28: 545-552, 2012.
APA
Liu, J., Zhang, Y., Xie, Y., Wang, F., Zhang, L., Deng, T., & Luo, H. (2012). 5-Aza-2'-deoxycytidine induces cytotoxicity in BGC-823 cells via DNA methyltransferase 1 and 3a independent of p53 status. Oncology Reports, 28, 545-552. https://doi.org/10.3892/or.2012.1838
MLA
Liu, J., Zhang, Y., Xie, Y., Wang, F., Zhang, L., Deng, T., Luo, H."5-Aza-2'-deoxycytidine induces cytotoxicity in BGC-823 cells via DNA methyltransferase 1 and 3a independent of p53 status". Oncology Reports 28.2 (2012): 545-552.
Chicago
Liu, J., Zhang, Y., Xie, Y., Wang, F., Zhang, L., Deng, T., Luo, H."5-Aza-2'-deoxycytidine induces cytotoxicity in BGC-823 cells via DNA methyltransferase 1 and 3a independent of p53 status". Oncology Reports 28, no. 2 (2012): 545-552. https://doi.org/10.3892/or.2012.1838
Copy and paste a formatted citation
x
Spandidos Publications style
Liu J, Zhang Y, Xie Y, Wang F, Zhang L, Deng T and Luo H: 5-Aza-2'-deoxycytidine induces cytotoxicity in BGC-823 cells via DNA methyltransferase 1 and 3a independent of p53 status. Oncol Rep 28: 545-552, 2012.
APA
Liu, J., Zhang, Y., Xie, Y., Wang, F., Zhang, L., Deng, T., & Luo, H. (2012). 5-Aza-2'-deoxycytidine induces cytotoxicity in BGC-823 cells via DNA methyltransferase 1 and 3a independent of p53 status. Oncology Reports, 28, 545-552. https://doi.org/10.3892/or.2012.1838
MLA
Liu, J., Zhang, Y., Xie, Y., Wang, F., Zhang, L., Deng, T., Luo, H."5-Aza-2'-deoxycytidine induces cytotoxicity in BGC-823 cells via DNA methyltransferase 1 and 3a independent of p53 status". Oncology Reports 28.2 (2012): 545-552.
Chicago
Liu, J., Zhang, Y., Xie, Y., Wang, F., Zhang, L., Deng, T., Luo, H."5-Aza-2'-deoxycytidine induces cytotoxicity in BGC-823 cells via DNA methyltransferase 1 and 3a independent of p53 status". Oncology Reports 28, no. 2 (2012): 545-552. https://doi.org/10.3892/or.2012.1838
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