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Effects of 5-aza-2ˈ-deoxycytidine and valproic acid on epigenetic-modifying dnmt1 gene expression, cell growth inhibition and apoptosis induction in hepatocellular carcinoma wch-17 cell line
Introduction
dna molecule of the eukaryotic cells is found in the form of a nucleoprotein complex named chromatin. in fact, the genome of the cells is divided into two components, including euchromatin and hetero-chromatin. two epigenetic modifications are critical for transcriptional control of genes, acetylation of the amino-terminal tails of histones h3 and h4 by histone acetyltransferases (hats) and dna methylation by dna methyltransfrases (dnmts). dna methylation is associated with gene inactivity and transcriptional silencing. histone deacetylation performed by histone deacetylases (hdacs) plays an important role in cancer induction and tumorigenesis. hypermethylation of tumor suppressor genes is catalyzed by various methyltransferase (nmt) enzymes, including dnmt1, dnmt2 and dnmt3. the most well characterized dna dmetilating drugs is 5-aza-2ˈ-deoxycytidine (5-aza-cdr) which inhibits dna cytosine methylation and reactivates silenced genes. histone deacetylase inhibitor valproic acid (vpa) inhibits histone deacetylases resulting apoptosis induction. the aim of the present study was to analyze the effect of 5-aza-cdr (as dna demetilating agent) and vpa (as histone deacetylase inhibitor) on the cell growth, apoptosis and dnmt1 gene expression in the hepatocellular carcinoma wch-17 cell line.
Methods
Materials and methods: mtt assay, flow cytometry assay and quantitative real-time rt-pcr were performed to evaluate the viability and apoptotic effects of the compounds and also dnmt1 gene expression respectively.
Results
Results: 5-aza-cdr and vpa inhibited the growth of wch-17 cell and induced apoptosis significantly with a time- and dose-dependent manner and also 5-aza-cdr down-regulated dnmt1 gene expression significantly.
Conclusion
Conclusion: 5-aza-cdr and vpa can significantly inhibit the growth of wch-17 cell and play a significant role in apoptosis induction and also 5-aza-cdr can decrease dnmt1 gene expression.
