Cordycepin induces autophagy-mediated c-FLIPL degradation and leads to apoptosis in human non-small cell lung cancer cells.
Cordycepin induces autophagy-mediated c-FLIPL degradation and leads to apoptosis in human non-small cell lung cancer cells.
复制标题
虫草素诱导自噬介导的 c-FLIPL 降解并导致人非小细胞肺癌细胞凋亡。
DOI：
10.18632/oncotarget.14262
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发表时间：
2017-01-24
期刊：
影响因子：
--
通讯作者：
Su L
中科院分区：
文献类型：
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作者：
Yu X;Ling J;Liu X;Guo S;Lin Y;Liu X;Su L
虫草素是从蛹虫草中提取的主要活性成分，据报道对多种癌症类型具有抗肿瘤活性。然而，虫草素对人非小细胞肺癌细胞的作用仍不清楚。我们目前的工作表明，虫草素通过诱导人非小细胞肺癌细胞凋亡和自噬来抑制细胞生长。进一步的研究表明，虫草素引发与 c-FLIPL 下调相关的外源性细胞凋亡，从而抑制 caspase-8 的活性。 c-FLIPL 的异位表达显着阻止了虫草素引起的细胞凋亡。同时，虫草素通过抑制肺癌细胞中的mTOR信号通路来刺激自噬。当Atg5 siRNA或PI3K抑制剂LY294002阻断自噬时，虫草素引起的细胞凋亡水平明显减弱。此外，抑制自噬还可以升高c-FLIPL的水平，这表明虫草素触发的自噬促进了c-FLIPL的降解。因此，我们得出结论，虫草素通过自噬介导的 c-FLIPL 下调人 NSCLC 细胞诱导细胞凋亡。总而言之，我们的研究结果为虫草素的抗肿瘤特性提供了新的前景，这可能进一步促使虫草素成为非小细胞肺癌治疗中一种有前途的治疗方法。
Cordycepin, a main active composition extracted from Cordyceps militaris, has been reported to exert anti-tumor activity in a broad spectrum of cancer types. However, the function of cordycepin on human non-small cell lung cancer cells is still obscure. Our present work showed that cordycepin inhibited cell growth by inducing apoptosis and autophagy in human NSCLC cells. Further study revealed that cordycepin triggered extrinsic apoptosis associated with down-regulation of c-FLIPL which suppresses the activity of caspase-8. And ectopic expression of c-FLIPL dramatically prevented cordycepin-caused apoptosis. Meanwhile, cordycepin stimulated autophagy through suppressing mTOR signaling pathway in lung cancer cells. When autophagy was blocked by Atg5 siRNA or PI3K inhibitor LY294002, the levels of apoptosis caused by cordycepin were obviously attenuated. In addition, suppression of autophagy could also elevate the level of c-FLIPL which indicated cordycepin-triggered autophagy promoted the degradation of c-FLIPL. Therefore, we conclude that cordycepin induces apoptosis through autophagy-mediated downregulation of c-FLIPL in human NSCLC cells. Taken together, our findings provide a novel prospect on the anti-tumor property of cordycepin, which may further prompt cordycepin to serve as a promising therapeutic approach in NSCLC treatment.