Isoliquiritigenin Induces Mitochondrial Dysfunction and Apoptosis by Inhibiting mitoNEET in a Reactive Oxygen Species-Dependent Manner in A375 Human Melanoma Cells
Isoliquiritigenin Induces Mitochondrial Dysfunction and Apoptosis by Inhibiting mitoNEET in a Reactive Oxygen Species-Dependent Manner in A375 Human Melanoma Cells
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异甘草素通过以活性氧依赖性方式抑制 A375 人黑色素瘤细胞中的 mitoNEET 诱导线粒体功能障碍和细胞凋亡
DOI：
10.1155/2019/9817576
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发表时间：
2019-01-21
影响因子：
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通讯作者：
Zheng, Qiu-Sheng
中科院分区：
文献类型：
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作者：
Chen, Xiao-Yu;Ren, Huan-Huan;Zheng, Qiu-Sheng
线粒体蛋白mitoNEET是一种定位于线粒体外膜的铁硫蛋白，参与多种人类病理，包括囊性纤维化、糖尿病、肌肉萎缩和神经变性。在本研究中，我们发现光叶甘草根的成分之一异甘草素（Isoliquiiritigenin，ISL），可降低A375黑色素瘤细胞中mitoNEET的表达。我们还证明了mitoNEET可以调节活性氧（ROS）的含量，通过显示ISL介导的细胞ROS含量的增加可以通过mitoNEET过表达来减轻。我们还证实了ROS在ISL处理的A375细胞中的重要作用。在A375细胞中过表达mitoNEET可减轻凋亡率的增加和线粒体膜电位的降低。这些结果表明，ISL可以降低mitoNEET的表达，从而调节ROS含量，并随后诱导线粒体功能障碍和凋亡的A375细胞。我们的研究结果还强调了mitoNEET作为癌症治疗的一个有前途的线粒体靶点。
The mitochondrial protein mitoNEET is a type of iron-sulfur protein localized to the outer membrane of mitochondria and is involved in a variety of human pathologies including cystic fibrosis, diabetes, muscle atrophy, and neurodegeneration. In the current study, we found that isoliquiritigenin (ISL), one of the components of the root of Glycyrrhiza glabra L., could decrease the expression of mitoNEET in A375 melanoma cells. We also demonstrated that mitoNEET could regulate the content of reactive oxygen species (ROS), by showing that the ISL-mediated increase in the cellular ROS content could be mitigated by the mitoNEET overexpression. We also confirmed the important role of ROS in ISL-treated A375 cells. The increased apoptosis rate and the decreased mitochondrial membrane potential were mitigated by the overexpression of mitoNEET in A375 cells. These findings indicated that ISL could decrease the expression of mitoNEET, which regulated ROS content and subsequently induced mitochondrial dysfunction and apoptosis in A375 cells. Our findings also highlight mitoNEET as a promising mitochondrial target for cancer therapy.