Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles
Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles
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DOI：
10.1016/j.biomaterials.2011.10.080
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发表时间：
2012-02-01
期刊：
影响因子：
14
通讯作者：
Ahmad, Iqbal
中科院分区：
文献类型：
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作者：
Khan, Mohd Imran;Mohammad, Akbar;Ahmad, Iqbal
近年来，自噬在肿瘤治疗中引起了极大的研究兴趣。现在我们报道了我们合成的氧化铁纳米颗粒选择性地诱导癌细胞(A549)而不是正常细胞(IMR-90)的自噬。同样值得注意的是，自噬与ROS的产生以及线粒体的损伤有关。NAC对ROS的保护清楚地表明ROS在自噬和细胞死亡的过度激活中的作用。3-MA对癌细胞的预处理也显示出对自噬的保护作用，并促进了细胞的存活。结果还表明，经典的mTOR通路参与了氧化铁纳米粒诱导A549细胞自噬的过程。我们的结果表明，裸露的氧化铁纳米颗粒对人癌细胞(A549)有显著的细胞毒性，但对正常的人肺成纤维细胞(IMR-90)没有明显的细胞毒性，换句话说，我们的纳米颗粒选择性地杀死癌细胞。这是令人鼓舞的结论，氧化铁纳米颗粒具有潜在的应用于生物医学，如肿瘤治疗，特别是通过诱导自噬介导的癌细胞死亡。(C)2011爱思唯尔有限公司。保留所有权利。
Autophagy has attracted a great deal of research interest in tumor therapy in recent years. An attempt was made in this direction and now we report that iron oxide NPs synthesized by us selectively induce autophagy in cancer cells (A549) and not in normal cells (IMR-90). It was also noteworthy that autophagy correlated with ROS production as well as mitochondrial damage. Protection of NAC against ROS clearly suggested the implication of ROS in hyper-activation of autophagy and cell death. Pre-treatment of cancer cells with 3-MA also exhibited protection against autophagy and promote cellular viability. Results also showed involvement of classical mTOR pathway in autophagy induction by iron oxide NPs in A549 cells. Our results had shown that bare iron oxide NPs are significantly cytotoxic to human cancer cells (A549) but not to the normal human lung fibroblast cells (IMR-90),In other words our nanoparticles selectively kill cancerous cells. It is encouraging to conclude that iron oxide NPs bear the potential of its applications in biomedicine, such as tumor therapy specifically by inducing autophagy mediated cell death of cancer cells. (C) 2011 Elsevier Ltd. All rights reserved.