Is the effect of Decitabine limited to hypomethylation and DNMTs?

Background: Histone modifications play a crucial role in chromatin structure. Among enzymes, which regulate these processes, histone deacetylases (HDACs) can remove acetyl groups from histone tails, thus increasing their interaction with DNA and leading to chromatin condensation. 5-Aza-2′-deoxycytidine (AZad) or Decitabine is a potent hypomethylating agent that incorporates into DNA and traps DNA methyltransferase in the form of a covalent protein–DNA adduct. Azad, not only change the gene expression through demethylation of the gene's promoter, but it also can change gene expression independently from DNA demethylation. So, the present study was to distinguish whether AZad in addition to inhibitory effects on DNA methyltransferase, can change HDAC3 and HDAC7 mRNA expression in NALM-6, HL-60 cancer cell lines. Methods: HL-60, NALM-6 and normal cells were cultured, and the treatment dose of the AZad was obtained (1µM) by the MTT test. Finally, HDAC3 and HDAC7 mRNA expression were measured by Real Time PCR in HL-60 and NALM-6 cancerous cells before and after treatment. In addition, HDAC3 and HDAC7 mRNA expression in un-treated HL-60 and NALM-6 cancerous cells were compared to the normal cells. Results: Our result revealed that expression of HDAC3 and HDAC7, in HL-60 and NALM-6 cells increases as compared to normal cells. After treatment of HL-60 and NALM-6 cells with AZad, HDAC3 and HDAC7 mRNA expression were decreased significantly. Conclusions: Our data showed, the effects of AZad are not limited to direct hypomethylation of DNMTs but it can indirectly affect other epigenetic factors, such as HDACs activity, through converging pathways. Keywords: HDAC3 ; HDAC7 ; HL-60; NALM-6 ; Decitabine ; AZad