• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cancer Cell International >Melatonin enhances TNF-α-mediated cervical cancer HeLa cells death via suppressing CaMKII/Parkin/mitophagy axis
【24h】

Melatonin enhances TNF-α-mediated cervical cancer HeLa cells death via suppressing CaMKII/Parkin/mitophagy axis

机译：褪黑素通过抑制CaMKII / Parkin /有丝分裂轴来增强TNF-α介导的宫颈癌HeLa细胞死亡

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Tumor necrosis factor-α (TNF-α) immunotherapy controls the progression of human cervical cancer. Here, we explored the detailed molecular mechanisms played by melatonin in human cervical cancer (HeLa cells) death in the presence of TNF-α injury, with a particular attention to the mitochondrial homeostasis. HeLa cells were incubated with TNFα and then cell death was determined via MTT assay, TUNEL staining, caspase ELISA assay and western blotting. Mitochondrial function was detected via analyzing mitochondrial membrane potential using JC-1 staining, mitochondrial oxidative stress using flow cytometry and mitochondrial apoptosis using western blotting. Our data exhibited that treatment with HeLa cells using melatonin in the presence of TNF-α further triggered cancer cell cellular death. Molecular investigation demonstrated that melatonin enhanced the caspase-9 mitochondrion death, repressed mitochondrial potential, increased ROS production, augmented mPTP opening rate and elevated cyt-c expression in the nucleus. Moreover, melatonin application further suppressed mitochondrial ATP generation via reducing the expression of mitochondrial respiratory complex. Mechanistically, melatonin augmented the response of HeLa cells to TNF-α-mediated cancer death via repressing mitophagy. TNF-α treatment activated mitophagy via elevating Parkin expression and excessive mitophagy blocked mitochondrial apoptosis, ultimately alleviating the lethal action of TNF-α on HeLa cell. However, melatonin supplementation could prevent TNF-α-mediated mitophagy activation via inhibiting Parkin in a CaMKII-dependent manner. Interestingly, reactivation of CaMKII abolished the melatonin-mediated mitophagy arrest and HeLa cell death. Overall, our data highlight that melatonin enhances TNF-α-induced human cervical cancer HeLa cells mitochondrial apoptosis via inactivating the CaMKII/Parkin/mitophagy axis.
机译：肿瘤坏死因子-α（TNF-α）免疫疗法控制人宫颈癌的进展。在这里，我们探讨了褪黑素在存在TNF-α损伤的人类宫颈癌（HeLa细胞）死亡中所发挥的详细分子机制，尤其要关注线粒体的体内平衡。将HeLa细胞与TNFα孵育，然后通过MTT分析，TUNEL染色，半胱天冬酶ELISA分析和蛋白质印迹确定细胞死亡。通过使用JC-1染色分析线粒体膜电位，使用流式细胞仪分析线粒体氧化应激和使用Western印迹法检测线粒体凋亡来检测线粒体功能。我们的数据显示，在存在TNF-α的情况下，使用褪黑素对HeLa细胞进行治疗会进一步触发癌细胞的死亡。分子研究表明，褪黑素增强了caspase-9线粒体的死亡，抑制了线粒体的潜力，增加了ROS的产生，增加了mPTP的开放率，并增加了细胞核中cyt-c的表达。此外，褪黑激素的应用通过减少线粒体呼吸复合物的表达进一步抑制了线粒体ATP的产生。从机制上讲，褪黑激素通过抑制线粒体吞噬增强了HeLa细胞对TNF-α介导的癌症死亡的反应。 TNF-α处理可通过升高Parkin表达来激活线粒体，而过多的线粒体会阻断线粒体凋亡，最终减轻TNF-α对HeLa细胞的致死作用。但是，褪黑激素补充剂可以通过以CaMKII依赖性方式抑制Parkin来阻止TNF-α介导的线粒体活化。有趣的是，CaMKII的重新激活消除了褪黑激素介导的线粒体停滞和HeLa细胞死亡。总体而言，我们的数据强调褪黑素通过使CaMKII / Parkin /线粒体轴失活来增强TNF-α诱导的人宫颈癌HeLa细胞线粒体凋亡。

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