Abstract
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5-Aza-2'-Deoxycytidine and CDDP Synergistically Induce Apoptosis in Renal Carcinoma Cells via Enhancing the APAF-1 Activity
by Xiaojun Zhu, Faxian Yi, Pengliang Chen, Ligang Chen, Xiaoli Zhang, Chunli Cao, Wanlong Tan
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Background: It has been reported that the hypermethylation of APAF-1, DAPK-1 and other tumor suppressive genes (TSGs) correlates with progression of renal cell carcinoma and exerts prognostic and diagnostic relevance in renal cell carcinoma. A recent study has confirmed that demethylation regulates the TSGs expression and proliferation of various types of cancer cells. The present study was to recognize a potential anti-tumor effect of 5-aza2'-deoxycytidine (DAC), a demethylation agent.
Methods: We evaluated the DNA demethylation by DAC in human renal carcinoma cells and determined the synergism of the demethylation with the toxicity of Cisplatin (CDDP), which is a commonly utilized anti-tumor agent for renal carcinoma.
Results: It was demonstrated that DAC promoted a significant global genomic demethylation and improved APAF-1 expression at both mRNA and protein levels. The DAC treatment deteriorated the CDDP-induced viability decreasing Caki or ACHN cells and synergized the apoptosis induction of CDDP in ACHN cells. The treatment with both DAC and CDDP promoted a significantly higher level of renal carcinoma cell apoptosis than singular DAC or CDDP treatment. The APAF-1 knockdown significantly inhibited the synergism of DAC with the CDDPinduced apoptosis in ACHN cells.
Conclusions: The present study confirmed that DAC demethylated the CpGs, particularly APAF-1 in renal carcinoma cells, and that the demethylation synergized the cytotoxity of CDDP in renal carcinoma cells via enhancing the CDDP-induced apoptosis.
DOI: 10.7754/Clin.Lab.2015.150429
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