Research Center for Non-Communicable Diseases, Jahrom University of Medical Sciences, Jahrom 7414846199, Iran.
Exp Oncol. 2020 Sep;42(3):183-187. doi: 10.32471/exp-oncology.2312-8852.vol-42-no-3.15113.
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.
组蛋白乙酰化和 DNA 甲基化等两种表观遗传修饰已被认为是基因调控的关键因素。许多实体瘤中都存在细胞因子信号转导家族抑制因子 SOCS-1 和 SOCS-3 的高甲基化和去乙酰化。此前，我们评估了 5-氮杂-2'-脱氧胞苷和丙戊酸对肝癌和结肠癌细胞的影响。
本研究旨在评估丙戊酸与 zebularine 对结肠癌 SW48 细胞系中 SOCS-1 和 SOCS-3 基因表达、细胞生长抑制和凋亡诱导的影响。
SW48 细胞用丙戊酸或 zebularine 处理 24 和 48 小时。评估化合物对细胞活力、SOCS-1 和 SOCS-3 基因表达和凋亡诱导的影响。应用逆转录聚合酶链反应分析和流式细胞术。
两种药物均以时间和剂量依赖的方式抑制细胞生长。在用丙戊酸（7.5 μM）处理的细胞中观察到凋亡效应，但在用 zebularine（75 μM）处理的细胞中未观察到。丙戊酸而非 zebularine 上调 SOCS-1 和 SOCS-3 基因表达。
表观遗传调控可通过组蛋白乙酰化重新激活沉默的肿瘤抑制基因 SOCS-1 和 SOCS-3，从而诱导细胞凋亡。
