Abstract
Objective: DNA methylation, the covalent addition of a methyl group to cytosine, and histone modification play an important role in the establishment and maintenance of the program of gene expression. The balance of histone acetylation is determined by the activities of two groups of enzymes including histone acetyltransferases (HATs) and histone deacetylases (HDACs). Histone deacetylation is generally associated with silencing gene expression resulting in several solid tumors. HDAC inhibitors (HDACIs) are the new class of potential anticancer compounds for the treatment of the solid and hematological cancers. The current study was designed to evaluate the effect of trichostatin A (TSA) on histone deacetylases 1, 2 and 3, p21Cip1/Waf1/Sdi1 (p21), p27Kip1 (p27), and p57Kip2 (p57) gene expression in breast cancer SK-BR-3 cell line. Materials and Methods: The breast cancer SK-BR-3 line was treated with TSA. To determine cell viability, cell apoptosis, and the relative expression level of the genes, MTT assay, cell apoptosis assay, and qRT-PCR were done respectively. Results: TSA significantly inhibited cell growth, and induced apoptosis. Furthermore, this compound increased p21, p27, and p57 and decreased histone deacetylases 1, 2 and 3 gene expression significantly. Conclusion: The TSA can reactivate the p21, p27, and p57 through down-regulation of histone deacetylases 1, 2 and 3 gene expression.
Highlights
DNA methylation, the covalent addition of a methyl group to cytosine, and histone modification play an important role in the establishment and maintenance of the program of gene expression
We report that trichostatin A (TSA) can down-regulate histone deacetylases (HDACs) 1, 2, and 3 and up-regulate p21, p27, and p57 resulting in cell growth inhibition and apoptosis induction in breast cancer SK-BR-3 cell line
It has been reported that HDACs suppresses the growth of breast cancer cell MCF-7, induce apoptosis, and arrested G1 phase of MCF-7 cells by p21 up-regulation and cyclin D1 down-regulation [20]
Summary
DNA methylation, the covalent addition of a methyl group to cytosine, and histone modification play an important role in the establishment and maintenance of the program of gene expression. Hypermethylation of tumor suppressor genes (TSGs) are well documented in various cancers [1].The balance of histone acetylation and deactylation is determined by the activities of two groups of enzymes including histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs include a family of 18 genes, which are grouped into classes I–IV based on their homology to their respective yeast orthologues. Mammillary Cell cycle progression is a regulated process that involves several checkpoints that assess extracellular signals and DNA integrity. Cyclins and their partner, cyclin-dependent kinases (CDKs), are positive regulators of cell cycle progression; whereas CDK inhibitors (CDKIs) are important negative regulators.
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