Abstract
Decitabine is a potent anticancer hypomethylating agent and changes the gene expression through the gene's promoter demethylation and also independently from DNA demethylation. So, the present study was designed to distinguish whether Decitabine, in addition to inhibitory effects on DNA methyltransferase, can change HDAC3 and HDAC7 mRNA expression in NALM-6 and HL-60 cancer cell lines. HL-60, NALM-6, and normal cells were cultured, and the Decitabine treatment dose was obtained (1 µM) through the MTT assay. Finally, HDAC3 and HDAC7 mRNA expression were measured by Real-Time PCR in HL-60 and NALM-6 cancerous cells before and after treatment. Furthermore, HDAC3 and HDAC7 mRNA expression in untreated HL-60 and NALM-6 cancerous cells were compared to normal cells. Our results revealed that the 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 Decitabine, HDAC3, and HDAC7 mRNA expression were decreased significantly. Our data confirmed that the effects of Decitabine are not limited to direct hypomethylation of DNMTs, but it can indirectly affect other epigenetic factors, such as HDACs activity, through converging pathways.
Highlights
Epigenetics changes mean gene function cannot be explained by changes in DNA sequences[1]
The inhibitory effect of Decitabine was evaluated on the Hl-60 and NALM-6 cells proliferation, followed by manual cell counting after 24, 48, and 72 hours
The results show that the expression of the HDAC3 gene was significantly reduced in Hl-60 and NALM-6 cell lines after Decitabine treatment (1 μM)
Summary
Epigenetics changes mean gene function cannot be explained by changes in DNA sequences[1]. There are multiple types of epigenetic mechanisms, such as non-coding RNA regulation, DNA methylation, and histone modifications. Histone modifications are regulated by multiple enzymes, including methyltransferases (HMTs), demethylase (HDM), acetyltransferase (HATs), and deacetylases (HDACs) [2, 4]. The present study was designed to distinguish whether Decitabine, in addition to inhibitory effects on DNA methyltransferase, can change HDAC3 and HDAC7 mRNA expression in NALM-6 and HL-60 cancer cell lines. HDAC3 and HDAC7 mRNA expression in untreated HL-60 and NALM-6 cancerous cells were compared to normal cells. After treatment of HL-60 and NALM-6 cells with Decitabine, HDAC3, and HDAC7 mRNA expression were decreased significantly. Conclusions: Our data confirmed that the effects of Decitabine are not limited to direct hypomethylation of DNMTs, but it can indirectly affect other epigenetic factors, such as HDACs activity, through converging pathways
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