Effect of valproic acid and zebularine on SOCS-1 and SOCS-3 gene expression in colon carcinoma SW48 cell line.

Abstract

Two epigenetic modifications such as histone acetylation and DNA methylation have been known as critical players of gene regulation. Hypermethylation and deacetylation of suppressors of cytokine signaling family SOCS-1and SOCS-3have been shown in many solid cancers. Previously, we evaluated the effect of 5-aza-2'-deoxycytidine and valproic acid on hepatocellular carcinoma and colon cancer cells. The present study was designed to assess the effect of valproic acid in comparison to zebularine on SOCS-1and SOCS-3gene expression, cell growth inhibition and apoptosis induction in colon carcinoma SW48cell line. SW48cells were treated with valproic acid or zebularine for 24h and 48h. The effect of the compounds on cell viability, SOCS-1and SOCS-3gene expression, and apoptosis induction was evaluated. Reverse transcription polymerase chain reaction analysis and flow cytometry were applied. Both agents inhibited cell growth in a time- and dose-dependent fashion. The apoptotic effect was observed in cells treated with valproic acid (7.5μM) but not zebularine (75μM). The valproic acid but not zebularine upregulated SOCS-1 and SOCS-3gene expression. Epigenetic modulation can reactivate silenced tumor suppressor genes SOCS-1and SOCS-3through histone acetylation resulting in apoptosis induction.