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

  • Published online on: May 29, 2012     https://doi.org/10.3892/or.2012.1838
  • Pages: 545-552
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

August 2012
Volume 28 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

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