Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhi Road, Daping Yuzhong District, Chongqing 400042, China.
Biomed Res Int. 2014;2014:696107. doi: 10.1155/2014/696107. Epub 2014 Jan 27.
Ebselen a selenoorganic compound showing glutathione peroxidase like activity is an anti-inflammatory and antioxidative agent. Its cytoprotective activity has been investigated in recent years. However, experimental evidence also shows that ebselen causes cell death in several cancer cell types whose mechanism has not yet been elucidated. In this study, we examined the effect of ebselen on multiple myeloma (MM) cell lines in vitro. The results showed that ebselen significantly enhanced the production of reactive oxygen species (ROS) accompanied by cell viability decrease and apoptosis rate increase. Further studies revealed that ebselen can induce Bax redistribution from the cytosol to mitochondria leading to mitochondrial membrane potential ΔΨm changes and cytochrome C release from the mitochondria to cytosol. Furtherly, we found that exogenous addition of N-acetyl cysteine (NAC) completely diminished the cell damage induced by ebselen. This result suggests that relatively high concentration of ebselen can induce MM cells apoptosis in culture by enhancing the production of endogenous ROS and triggering mitochondria mediated apoptotic pathway.
依布硒啉是一种具有谷胱甘肽过氧化物酶样活性的有机硒化合物，具有抗炎和抗氧化作用。近年来，其细胞保护活性已得到研究。然而，实验证据也表明，依布硒啉会导致几种癌细胞死亡，但其机制尚未阐明。在这项研究中，我们研究了依布硒啉对体外多发性骨髓瘤（MM）细胞系的影响。结果表明，依布硒啉可显著增加活性氧（ROS）的产生，同时降低细胞活力并增加细胞凋亡率。进一步的研究表明，依布硒啉可诱导 Bax 从细胞质向线粒体重定位，导致线粒体膜电位ΔΨm 变化和细胞色素 C 从线粒体释放到细胞质。此外，我们发现，外源性添加 N-乙酰半胱氨酸（NAC）可完全消除依布硒啉引起的细胞损伤。这一结果表明，相对较高浓度的依布硒啉可以通过增强内源性 ROS 的产生并触发线粒体介导的凋亡途径，诱导 MM 细胞在培养中凋亡。
