韦德尔内酯靶向套细胞淋巴瘤中的 EZH2 介导的组蛋白 H3K27 甲基化。
Wedelolactone Targets EZH2-mediated Histone H3K27 Methylation in Mantle Cell Lymphoma.
机构信息
Latvian Institute of Organic Synthesis, Riga, Latvia
Latvian Institute of Organic Synthesis, Riga, Latvia.
出版信息
Anticancer Res. 2019 Aug;39(8):4179-4184. doi: 10.21873/anticanres.13577.
BACKGROUND/AIM: Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2), possesses histone N-methyltransferase (HMT) activity and plays an essential role in cancer initiation and development. The aim of the present study was to investigate the potential of Wedelolactone (WL) to inhibit the methylation activity of EZH2.
MATERIALS AND METHODS
The mantle cell lymphoma (MCL) cell line, Mino, was treated with WL, while untreated cells were used as control. HMT activity and EZH2 amount were measured in nuclear extracts from WL-treated and control Mino cells.
RESULTS
WL was found to target EZH2-mediated histone H3K27 methylation. Along with the inhibition of H3K27 methylation in vitro (IC50=0.3 μM), WL suppressed HMT activity in Mino cells with an IC50 value of 3.2 μM. We detected a reduced amount of EZH2 in Mino cells treated with WL, compared to untreated control cells.
CONCLUSION
This is the first study to show that WL induces inhibition of H3K27 methylation via EZH2 modulation and decreases cell proliferation in MCL, in vitro. WL is proposed as a promising agent and a novel epigenetic approach in MCL investigation and treatment.
背景/目的：EZH2（多梳抑制复合物 2（PRC2）的催化亚基）是组蛋白 N-甲基转移酶（HMT）活性，在癌症的发生和发展中起着重要作用。本研究旨在探讨冬凌草甲素（WL）抑制 EZH2 甲基化活性的潜力。
材料与方法
用 WL 处理套细胞淋巴瘤（MCL）细胞系 Mino，未处理的细胞作为对照。用核提取物测量 WL 处理和对照 Mino 细胞中的 HMT 活性和 EZH2 含量。
结果
发现 WL 靶向 EZH2 介导的组蛋白 H3K27 甲基化。与体外抑制 H3K27 甲基化（IC50=0.3 μM）一致，WL 在 3.2 μM 的 IC50 值下抑制 Mino 细胞中的 HMT 活性。与未处理的对照细胞相比，我们在 WL 处理的 Mino 细胞中检测到 EZH2 含量减少。
结论
这是第一项表明 WL 通过 EZH2 调节诱导 H3K27 甲基化抑制并减少体外 MCL 细胞增殖的研究。WL 被提议作为一种有前途的药物和一种新的表观遗传方法，用于 MCL 的研究和治疗。
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