Ciclopirox targets cellular bioenergetics and activates ER stress to induce apoptosis in non-small cell lung cancer cells.
Ciclopirox targets cellular bioenergetics and activates ER stress to induce apoptosis in non-small cell lung cancer cells.
复制标题
环吡酮以细胞生物能学为靶点，激活内质网应激，诱导非小细胞肺癌细胞凋亡。
DOI：
10.1186/s12964-022-00847-x
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发表时间：
2022-03-24
期刊：
影响因子：
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通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Lu J;Li Y;Gong S;Wang J;Lu X;Jin Q;Lu B;Chen Q
目前，肺癌仍然是与癌症相关的主要原因。实体瘤和体内的血液系统恶性肿瘤。
CCK-8使用克隆的形成和细胞循环检测来观察抑制剂对NSCLC细胞的增殖能力的影响。切片，葡萄糖摄取，氧气消费率（OCR）和细胞外酸化率（ECAR）实验用于检查蛋白质变化。
我们报告，CPX通过抑制上皮 - 间质转变，抑制NSCLC细胞的迁移和侵袭能力，损害细胞生物能力，并促进活性氧激活内质网（ERH）的重量诱导的室内型细胞死亡。
我们的研究表明，CPX靶向细胞生物能学并激活ER中未折叠的蛋白质反应以驱动NSCLC细胞中的凋亡，这表明CPX可能是治疗NSCLC的潜在治疗药物。
视频摘要
在线版本中包含10.1186/s12964-022-00847-X的补充材料。
Lung cancer remains a major cause of cancer-related mortality throughout the world at present. Repositioning of existing drugs for other diseases is a promising strategy for cancer therapies, which may rapidly advance potentially promising agents into clinical trials and cut down the cost of drug development. Ciclopirox (CPX), an iron chelator commonly used to treat fungal infections, which has recently been shown to have antitumor activity against a variety of cancers including both solid tumors and hematological malignancies in vitro and in vivo. However, the effect of CPX on non-small cell lung cancer (NSCLC) and the underlying mechanism is still unclear. CCK-8, clonal formation test and cell cycle detection were used to observe the effect of inhibitor on the proliferation ability of NSCLC cells. The effects of CPX on the metastasis ability of NSCLC cells were analyzed by Transwell assays. Apoptosis assay was used to observe the level of cells apoptosis. The role of CPX in energy metabolism of NSCLC cells was investigated by reactive oxygen species (ROS) detection, glucose uptake, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) experiments. Western blot was used to examine the protein changes. We report that CPX inhibits NSCLC cell migration and invasion abilities through inhibiting the epithelial-mesenchymal transition, impairing cellular bioenergetics, and promoting reactive oxygen species to activate endoplasmic reticulum (ER) stress-induced apoptotic cell death. Moreover, CPX intraperitoneal injection can significantly inhibit NSCLC growth in vivo in a xenograft model. Our study revealed that CPX targets cellular bioenergetics and activates unfolded protein response in ER to drive apoptosis in NSCLC cells, indicating that CPX may be a potential therapeutic drug for the treatment of NSCLC. Video Abstract The online version contains supplementary material available at 10.1186/s12964-022-00847-x.
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影响因子：
5.4
作者：
Baer A;Lundberg L;Swales D;Waybright N;Pinkham C;Dinman JD;Jacobs JL;Kehn-Hall K
通讯作者：
Kehn-Hall K
影响因子：
5.3
作者：
Jaronen M;Goldsteins G;Koistinaho J
通讯作者：
Koistinaho J
影响因子：
21.3
作者：
Tabas, Ira;Ron, David
通讯作者：
Ron, David
影响因子：
20.3
作者：
Eberhard, Yanina;McDermott, Sean P.;Schimmer, Aaron D.
通讯作者：
Schimmer, Aaron D.
DOI：
10.1038/nrm3758
发表时间：
2014-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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