• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Oncotarget >Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells
【2h】

Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells

机译：活性氧水平升高导致穿心莲内酯治疗的结肠癌细胞产生内质网应激和细胞毒性

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Chemotherapy continues to play an essential role in the management of many cancers including colon cancer, the third leading cause of death due to cancer in the United States. Many naturally occurring plant compounds have been demonstrated to possess anti-cancer cell activity and have the potential to supplement existing chemotherapy strategies. The plant metabolite andrographolide induces cell death in cancer cells and apoptosis is dependent upon the induction of endoplasmic reticulum stress (ER stress) leading to the unfolded protein response (UPR). The goal of the present study was to determine the mechanism by which andrographolide induces ER stress and to further evaluate its role in promoting cell death pathways. The T84 and COLO 205 cancer cell lines were used to demonstrate that andrographolide induces increased ROS levels, corresponding anti-oxidant response molecules, and reduced mitochondrial membrane potential. No increases in ROS levels were detected in control colon fibroblast cells. Andrographolide-induced cell death, UPR signaling, and CHOP, Bax, and caspase 3 apoptosis elements were all inhibited in the presence of the ROS scavenger NAC. Additionally, andrographolide-induced suppression of cyclins B1 and D1 were also reversed in the presence of NAC. Finally, Akt phosphorylation and phospho-mTOR levels that are normally suppressed by andrographolide were also expressed at normal levels in the absence of ROS. These data demonstrate that andrographolide induces ER stress leading to apoptosis through the induction of ROS and that elevated ROS also play an important role in down-regulating cell cycle progression and cell survival pathways as well.
机译：化学疗法在许多癌症（包括结肠癌）的管理中继续发挥重要作用，结肠癌是美国癌症导致的第三大死亡原因。已证明许多天然存在的植物化合物具有抗癌细胞活性，并有可能补充现有的化学疗法。植物代谢物穿心莲内酯诱导癌细胞死亡，细胞凋亡取决于内质网应激（ER应激）的诱导，导致未折叠的蛋白质反应（UPR）。本研究的目的是确定穿心莲内酯诱导内质网应激的机制，并进一步评估其在促进细胞死亡途径中的作用。 T84和COLO 205癌细胞系用于证明穿心莲内酯诱导ROS水平升高，相应的抗氧化反应分子和线粒体膜电位降低。在对照结肠成纤维细胞中未检测到ROS水平的增加。在ROS清道夫NAC的存在下，穿心莲内酯诱导的细胞死亡，UPR信号传导，CHOP，Bax和caspase 3凋亡均被抑制。此外，在NAC存在下，穿心莲内酯对细胞周期蛋白B1和D1的抑制作用也被逆转。最后，在没有ROS的情况下，通常被穿心莲内酯抑制的Akt磷酸化和磷酸-mTOR水平也以正常水平表达。这些数据表明穿心莲内酯通过诱导ROS诱导内质网应激从而导致细胞凋亡，而升高的ROS在下调细胞周期进程和细胞存活途径中也起着重要作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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