S-烯丙半胱氨酸通过 DNMT1 抑制卵巢癌细胞增殖的 DNA 甲基化。
S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1.
机构信息
Hangzhou Translational Medicine Research Center, Zhejiang Chinese Medical University, Hangzhou First People's Hospital, No.261 Huansha Road, Shangcheng District, Hangzhou, 310006, China.
College of Pharmaceutical Science, Zhejiang Chinese Medical University, No.548 Binwen Road, Binjiang District, Hangzhou, 310053, China.
出版信息
J Ovarian Res. 2018 May 14;11(1):39. doi: 10.1186/s13048-018-0412-1.
BACKGROUND
The anti-tumor effects of S-allylcysteine (SAC), a water-soluble garlic derivative, on human ovarian cancer cells have been previous studied in vitro and in vivo models but the precise epigenetic molecular mechanisms are still unclear. This study aimed to investigate the epigenetic mechanism of SAC.
METHODS
Human epithelial ovarian cancer cell line A2780 was selected. Cell proliferation and cell cycle was analyzed. DNA methylation, DNA methyltransferase (DNMT) activity, tumor suppressor gene expressions, as well as protein expression were analyzed.
RESULTS
SAC could inhibit the proliferation of A2780 cells in dose- and time-dependent manners (the IC was 16.25 mmol/L and 5.25 mmol/L at 48 h and 72 h). Treatment of A2780 cells with SAC resulted in G1/S phase arrest. SAC treatment decreased global DNA methylation levels in A2780 cells in a dose-dependent manner. SAC decreased the levels of 5-methylcytosine, DNMT activity, messenger RNA (mRNA) and protein levels of DNMT1. Additionally, SAC treatment resulted in re-expression of the mRNA and proteins of silenced tumor suppressor gene CDKN1A accompany with reduced cell division control 2 expression.
CONCLUSION
Our data indicated the potential therapeutic effects of SAC on the human ovarian carcinoma cell line A2780 in vitro. The epigenetic mechanism of action of SAC may have important implications for epigenetic therapy.
背景
水溶性大蒜衍生物 S-烯丙半胱氨酸（SAC）对人卵巢癌细胞的抗肿瘤作用已在体外和体内模型中进行了研究，但确切的表观遗传分子机制仍不清楚。本研究旨在探讨 SAC 的表观遗传机制。
方法
选择人上皮性卵巢癌细胞系 A2780。分析细胞增殖和细胞周期。分析 DNA 甲基化、DNA 甲基转移酶（DNMT）活性、肿瘤抑制基因表达以及蛋白质表达。
结果
SAC 可呈剂量和时间依赖性地抑制 A2780 细胞的增殖（48 小时和 72 小时的 IC 分别为 16.25mmol/L 和 5.25mmol/L）。SAC 处理 A2780 细胞导致 G1/S 期阻滞。SAC 处理以剂量依赖性方式降低 A2780 细胞中的全基因组 DNA 甲基化水平。SAC 降低了 5-甲基胞嘧啶、DNMT 活性、信使 RNA（mRNA）和 DNMT1 蛋白水平。此外，SAC 处理导致沉默的肿瘤抑制基因 CDKN1A 的 mRNA 和蛋白重新表达，同时细胞分裂控制 2 表达降低。
结论
我们的数据表明 SAC 对体外人卵巢癌细胞系 A2780 具有潜在的治疗作用。SAC 的表观遗传作用机制可能对表观遗传治疗具有重要意义。
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