Effect of valproic acid on SOCS-1, SOCS-2, SOCS-3, SOCS-5, SOCS6, and SOCS-7 genes expression and cell growth inhibition in colon carcinoma
Gastroenterology and Hepatology from Bed to Bench,
Backgrounds: Cancer is a process induced by the accumulation of epigenetic alterations such as DNA methylation and histone deacetylation. The DNA methylation and histone deacetylation of tumor suppressor genes (TSGs) have been shown in various cancers. Recent studies have shown that silencing of TSGs, resulting from epigenetic alterations such as deacetylation, is an early event in many human cancers. The methylation and deacetylation of suppressor of cytokine signaling (SOCS) family, as TSGs, have been demonstrated in numerous cancers. Histone deacetylase inhibitors (HDACIs) have emerged as the accessory therapeutic agents for human cancers, they can inhibit the activity of specific HDACs, restore the expression of some TSGs, and induce cell growth inhibition and apoptosis. The current study aimed to investigate the effect of valproic acid (VPA) on SOCS-1, SOCS-2, SOCS-3, SOCS-5, SOCS6, and SOCS-7 gene expression and cell growth inhibition in colon carcinoma IS1, IS2, and IS3 cell lines. Materials and Methods: The IS1, IS2, and IS3 cells were cultured and treated with VPA. To determine cell viability, cell apoptosis, and the relative gene expression level, MTT assay, flow cytometry assay, and qRT-PCR were done respectively. Results: VPA changed the expression level of the SOCS-1, SOCS-2, SOCS-3, SOCS-5, SOCS6, and SOCS-7 gene by which induced cell apoptosis and inhibit cell growth in all three cell lines, IS1, IS2, and IS3. Conclusion: VPA can induce apoptosis through reactivation of SOCS-1, SOCS-2, SOCS-3, SOCS-5, SOCS6, and SOCS-7 gene expression.
- valproic acid, SOCSs, apoptosis, colon carcinoma
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