...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemical Pharmacology >Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive oxygen species-dependent mitochondrial signaling pathway.
【24h】

Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive oxygen species-dependent mitochondrial signaling pathway.

机译：大黄素通过依赖于活性氧的线粒体信号传导途径诱导人肺腺癌细胞凋亡。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Emodin, a natural anthraquinone derivative isolated from Rheum palmatum L., has been reported to exhibit anti-cancer effect on several human cancers such as liver cancers and lung cancers. However, the molecular mechanisms of emodin-mediated tumor regression have not been fully defined. In this study, we show that treatment with 50 microM emodin resulted in a pronounced release of cytochrome c, activation of caspase-2, -3, and -9, and apoptosis in human lung adenocarcinoma A549 cells. These events were accompanied by the inactivation of ERK and AKT, generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential ((Delta)psi(m)), decrease of mitochondrial Bcl-2, and increase of mitochondrial Bax content. Ectopic expression of Bcl-2, or treatment with aurintricarboxylic acid, furosemide or caspase inhibitors markedly blocked emodin-induced apoptosis. Conversely, pharmacologic ERK and AKT inhibition promoted emodin-induced apoptosis. Furthermore, the free radical scavenger ascorbic acid and N-acetylcysteine attenuated emodin-mediated ROS production, ERK and AKT inactivation, mitochondrial dysfunction, Bcl-2/Bax modulation, and apoptosis. Take together, these findings suggest that in A549 cells, emodin-mediated oxidative injury acts as an early and upstream change in the cell death cascade to antagonize cytoprotective ERK and AKT signaling, triggers mitochondrial dysfunction, Bcl-2 and Bax modulation, mitochondrial cytochrome c release, caspase activation, and consequent leading to apoptosis.
机译：大黄素，一种从大黄掌中分离的天然蒽醌衍生物，据报道对几种人类癌症如肝癌和肺癌表现出抗癌作用。但是，大黄素介导的肿瘤消退的分子机制尚未完全确定。在这项研究中，我们显示了用50 microM大黄素处理可导致人肺腺癌A549细胞中细胞色素c的明显释放，caspase-2，-3和-9的活化以及细胞凋亡。这些事件伴随着ERK和AKT的失活，活性氧（ROS）的产生，线粒体膜电位（Δpsi（m））的破坏，线粒体Bcl-2的减少以及线粒体Bax含量的增加。 Bcl-2的异位表达，或用金三羧酸，速尿或半胱天冬酶抑制剂治疗可显着阻断大黄素诱导的细胞凋亡。相反，药理性ERK和AKT抑制促进大黄素诱导的细胞凋亡。此外，自由基清除剂抗坏血酸和N-乙酰半胱氨酸减弱了大黄素介导的大黄素介导的ROS产生，ERK和AKT失活，线粒体功能障碍，Bcl-2 / Bax调节和凋亡。综上所述，这些发现表明，在A549细胞中，大黄素介导的氧化损伤是细胞死亡级联反应的早期和上游变化，以拮抗细胞保护性ERK和AKT信号传导，触发线粒体功能障碍，Bcl-2和Bax调节，线粒体细胞色素c。释放，胱天蛋白酶激活，并因此导致凋亡。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号