title: 5-Aza-2'-Deoxycytidine and CDDP Synergistically Induce Apoptosis in Renal Carcinoma Cells via Enhancing the APAF-1 Activity.
abstract: 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-aza-2'-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 CDDP-induced 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.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhu
authors.forename: Faxian
authors.initials: F
authors.lastname: Yi
authors.forename: Pengliang
authors.initials: P
authors.lastname: Chen
authors.forename: Ligang
authors.initials: L
authors.lastname: Chen
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Chunli
authors.initials: C
authors.lastname: Cao
authors.forename: Wanlong
authors.initials: W
authors.lastname: Tan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1 / Q000032:analysis / Q000502:physiology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019175:DNA Methylation; D000077209:Decitabine; D004357:Drug Synergism; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: C506592:APAF1 protein, human; D000970:Antineoplastic Agents; D053477:Apoptotic Protease-Activating Factor 1; D000077209:Decitabine; D001374:Azacitidine; D002945:Cisplatin