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

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-1 and SOCS-3 have 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-1 and SOCS-3 gene expression, cell growth inhibition and apoptosis induction in colon carcinoma SW48 cell line. SW48 cells were treated with valproic acid or zebularine for 24 h and 48 h. The effect of the compounds on cell viability, SOCS-1 and SOCS-3 gene 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 (7.5 μM) but not zebularine (75 μM). The valproic acid but not zebularine upregulated SOCS-1 and SOCS-3 gene expression. Epigenetic modulation can reactivate silenced tumor suppressor genes SOCS-1 and SOCS-3 through histone acetylation resulting in apoptosis induction.