Apoptosis induced by ursodeoxycholic acid in human melanoma cells through the mitochondrial pathway
Apoptosis induced by ursodeoxycholic acid in human melanoma cells through the mitochondrial pathway
复制标题
熊去氧胆酸通过线粒体途径诱导人黑色素瘤细胞凋亡
DOI：
10.3892/or.2018.6828
复制
发表时间：
2018-10
期刊：
影响因子：
4.2
通讯作者：
Shen DY
中科院分区：
文献类型：
--
作者：
Yu H;Fu QR;Huang ZJ;Lin JY;Chen QX;Wang Q;Shen DY
熊去氧胆酸（UDCA）是从动物胆汁中提取的一种亲水性胆汁酸，具有广泛的生物学功能。本研究结果表明，UDCA可有效抑制两种人黑色素瘤细胞系（M14和A375）的增殖，并具有时间和浓度依赖性。不同浓度UDCA作用后，M14细胞出现典型的形态学改变，集落形成能力减弱。流式细胞仪分析表明，UDCA可诱导M14细胞线粒体膜电位降低和活性氧（ROS）水平升高。细胞周期阻滞在G2/M期，这是通过在蛋白水平上的细胞周期蛋白依赖性激酶1和cyclinB 1的减少证实的。而UDCA与caspase抑制剂Z-VAD-FMK联合作用后，M14细胞凋亡率明显降低。此外，研究表明UDCA通过ROS触发的细胞相关途径诱导人黑色素瘤M14细胞凋亡，表现为裂解型半胱天冬酶-3、裂解型半胱天冬酶-9、凋亡蛋白酶激活因子-1、裂解型聚（ADP-核糖）聚合酶1的表达增加以及与凋亡相关的B细胞淋巴瘤-2（Bcl-2）相关X蛋白/Bcl-2比值升高。因此，UDCA可能是一种潜在的治疗人类黑色素瘤的药物。
Ursodeoxycholic acid (UDCA) is a type of hydrophilic bile acid extracted from animal bile with a wide range of biological functions. The present results demonstrated that UDCA could effectively inhibit the proliferation of two human melanoma cell line (M14 and A375) with time- and concentration-dependence. Following exposure to various concentrations of UDCA, M14 cells exhibited typical morphological changes and weaker ability of colony forming. Flow cytometry analysis demonstrated that UDCA could induce a decrease of mitochondrial membrane potential and an increase in reactive oxygen species (ROS) levels in M14 cells. The cell cycle was arrested in the G2/M phase, which was confirmed by the decrease of cyclin-dependent kinase 1 and cyclinB1 at the protein level. However, when M14 cells were treated with UDCA and Z-VAD-FMK (caspase inhibitor) synchronously, the apoptosis rate of the cells was reduced significantly. In addition, it was demonstrated that UDCA induced apoptosis of human melanoma M14 cells through the ROS-triggered mitochondrial-associated pathway, which was indicated by the increased expression of cleaved-caspase-3, cleaved-caspase-9, apoptotic protease activating factor-1, cleaved-poly (ADP-ribose) polymerase 1 and the elevation of B cell lymphoma-2 (Bcl-2) associated X protein/Bcl-2 ratio associated with apoptosis. Therefore, UDCA may be a potential drug for the treatment of human melanoma.
登录
查看更多内容
影响因子：
3
作者：
T. Yokosuka;H. Goto;H. Fujii;T. Naruto;Masanobu Takeuchi;R. Tanoshima;Hiromi Kato;M. Yanagimachi;R. Kajiwara;S. Yokota
通讯作者：
T. Yokosuka;H. Goto;H. Fujii;T. Naruto;Masanobu Takeuchi;R. Tanoshima;Hiromi Kato;M. Yanagimachi;R. Kajiwara;S. Yokota
影响因子：
2
作者：
A. Jimenez-Sanchez
通讯作者：
A. Jimenez-Sanchez
影响因子：
4.2
作者：
Im, E;Martinez, JD
通讯作者：
Martinez, JD
影响因子：
11
作者：
Yadav PK;Tiwari M;Gupta A;Sharma A;Prasad S;Pandey AN;Chaube SK
通讯作者：
Chaube SK
影响因子：
4.5
作者：
Agarwal, Ayushi;Kasinathan, Akiladdevi;Sivalingam, Nageswaran
通讯作者：
Sivalingam, Nageswaran