Trichostatin A targets the mitochondrial respiratory chain, increasing mitochondrial reactive oxygen species production to trigger apoptosis in human breast cancer cells.
Trichostatin A targets the mitochondrial respiratory chain, increasing mitochondrial reactive oxygen species production to trigger apoptosis in human breast cancer cells.
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曲古抑菌素 A 靶向线粒体呼吸链，增加线粒体活性氧的产生，引发人乳腺癌细胞凋亡
DOI：
10.1371/journal.pone.0091610
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wu P
中科院分区：
文献类型：
--
作者：
Sun S;Han Y;Liu J;Fang Y;Tian Y;Zhou J;Ma D;Wu P
目的以组蛋白去乙酰化酶抑制剂（HDACIs）为基础的抗肿瘤药物具有诱导细胞凋亡、细胞周期阻滞、细胞分化和自噬等作用。然而，HDACI相关的抗肿瘤活性的机制尚未明确定义。本研究的目的是探讨曲古抑菌素A（TSA），一个经典的HDACI剂，对乳腺癌细胞的关键事件。方法采用集落形成和细胞活力测定法对MCF-7、MDA-MB-231和MCF-10A细胞系进行评价。流式细胞仪检测细胞凋亡及细胞周期分布。线粒体功能测定采用生化分析、流式细胞术和透射电镜。结果TSA抑制乳腺癌细胞的生长和增殖，对MCF-10A细胞无明显影响。TSA诱导的乳腺癌细胞凋亡由G2-M期阻滞启动，并依赖于线粒体呼吸链活性降低后产生的线粒体活性氧（ROS）。抗氧化剂如N-乙酰半胱氨酸（NAC）、还原型谷胱甘肽（GSH）和维生素C可明显减弱癌细胞线粒体ROS的产生和凋亡。结论TSA通过使细胞周期阻滞于G2-M期诱导细胞死亡，并依赖于线粒体呼吸链受损产生的ROS。
Aim Histone deacetylase inhibitors (HDACIs)-based therapies have stimulated interest via their anti-tumor activities, including apoptosis induction, cell cycle arrest, cell differentiation, and autophagy. However, the mechanisms of HDACI-associated anti-tumor activity are not yet clearly defined. The aim of this study was to explore the key events of Trichostatin A (TSA), a classic HDACI agent, against breast cancer cells. Methods The MCF-7, MDA-MB-231 and MCF-10A cell lines were evaluated with colony-forming and cell viability assays. Apoptosis and cell cycle distribution were detected by flow cytometry. Mitochondrial function was measured with biochemical assays, flow cytometry and transmission electron microscopy. Results TSA inhibited breast cancer cell viability and proliferation, without affecting MCF-10A cell. TSA-induced breast cancer cell apoptosis was initiated by G2-M arrest and depended on mitochondrial reactive oxygen species (ROS) produced subsequent to reduced mitochondrial respiratory chain activity. The enhanced mitochondrial ROS production and apoptosis in cancer cells were markedly attenuated by antioxidants, such as N-acetyl cysteine (NAC), reduced glutathione (GSH) and Vitamin C. Conclusion The present study demonstrated that TSA-induced cell death by arresting cell cycle in G2-M phase and was dependent on production of mitochondria-derived ROS, which was derived from impaired mitochondrial respiratory chain.
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影响因子：
16
作者：
de la Vega, Laureano;Grishina, Irina;Schmitz, M. Lienhard
通讯作者：
Schmitz, M. Lienhard
抑制Hec1表达增强人卵巢癌细胞对紫杉醇的敏感性
影响因子：
8.2
作者：
Mo, Qing-qing;Chen, Ping-bo;Chen, Gang
通讯作者：
Chen, Gang
影响因子：
4.8
作者：
Bernhard, D;Ausserlechner, MJ;Kofler, R
通讯作者：
Kofler, R
DOI：
10.1073/pnas.0607518103
发表时间：
2006-10-17
影响因子：
11.1
作者：
Xu, Weisheng;Ngo, Lang;Marks, Paul A.
通讯作者：
Marks, Paul A.
影响因子：
0.9
作者：
Lustberg, Maryam B;Ramaswamy, Bhuvaneswari
通讯作者：
Ramaswamy, Bhuvaneswari