Cordycepin induces autophagy-mediated c-FLIPL degradation and leads to apoptosis in human non-small cell lung cancer cells

作者: Xinghui Yu , Jianya Ling , Xianfang Liu , Sen Guo , Yidan Lin

DOI: 10.18632/ONCOTARGET.14262

关键词: LY294002ApoptosisImmunologyCell growthCancerCancer researchPI3K/AKT/mTOR pathwayATG5AutophagyCordycepinMedicine

摘要: // Xinghui Yu 1, * , Jianya Ling Xianfang Liu 2 Sen Guo 1 Yidan Lin 3 Xiangguo Su Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, University School Life Sciences, Jinan, China The Department Otolaryngology Head Neck Surgery, Hospital Affiliated to University, Thoracic Surgery West Hospital, Medical Sichuan Chengdu, These authors have contributed equally this work Correspondence to: Su, email: suling@sdu.edu.cn Keywords: apoptosis, c-FLIP, autophagy, cordycepin Received: June 16, 2016      Accepted: December 01, Published: 27, 2016 ABSTRACT Cordycepin, a main active composition extracted from Cordyceps militaris has been reported exert anti-tumor activity in broad spectrum cancer types. However, the function on human non-small cell lung cells is still obscure. Our present showed that inhibited growth by inducing apoptosis autophagy NSCLC cells. Further study revealed triggered extrinsic associated with down-regulation c-FLIP L which suppresses caspase-8. And ectopic expression dramatically prevented cordycepin-caused apoptosis. Meanwhile, stimulated through suppressing mTOR signaling pathway When was blocked Atg5 siRNA or PI3K inhibitor LY294002, levels caused were obviously attenuated. In addition, suppression could also elevate level indicated cordycepin-triggered promoted degradation . Therefore, we conclude induces autophagy-mediated downregulation Taken together, our findings provide novel prospect property cordycepin, may further prompt serve as promising therapeutic approach treatment.

参考文章(29)
Samira Goldar, Mahmoud Shekari Khaniani, Sima Mansoori Derakhshan, Behzad Baradaran, Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment Asian Pacific Journal of Cancer Prevention. ,vol. 16, pp. 2129- 2144 ,(2015) , 10.7314/APJCP.2015.16.6.2129
Yuanhong Liao, Jianya Ling, Guoying Zhang, Fengjun Liu, Shengce Tao, Zeguang Han, Saijuan Chen, Zhu Chen, Huangying Le, Cordycepin induces cell cycle arrest and apoptosis by inducing DNA damage and up-regulation of p53 in Leukemia cells Cell Cycle. ,vol. 14, pp. 761- 771 ,(2015) , 10.1080/15384101.2014.1000097
Jennings Xu, Xiuling Xu, Shaoqing Shi, Qiong Wang, Bryanna Saxton, Weiyang He, Xin Gou, Jun-Ho Jang, Toru Nyunoya, Xia Wang, Chengguo Xing, Lin Zhang, Yong Lin, Autophagy-Mediated Degradation of IAPs and c-FLIP(L) Potentiates Apoptosis Induced by Combination of TRAIL and Chal-24. Journal of Cellular Biochemistry. ,vol. 117, pp. 1136- 1144 ,(2016) , 10.1002/JCB.25397
Ling Gu, Liping Xie, Chuan Zuo, Zhigui Ma, Yanle Zhang, Yiping Zhu, Ju Gao, Targeting mTOR/p70S6K/glycolysis signaling pathway restores glucocorticoid sensitivity to 4E-BP1 null Burkitt Lymphoma BMC Cancer. ,vol. 15, pp. 529- 529 ,(2015) , 10.1186/S12885-015-1535-Z
Barbara Mojsa, Iréna Lassot, Solange Desagher, Mcl-1 ubiquitination: unique regulation of an essential survival protein Cells. ,vol. 3, pp. 418- 437 ,(2014) , 10.3390/CELLS3020418
Zhifen Yang, Daniel J Klionsky, Mammalian autophagy: core molecular machinery and signaling regulation Current Opinion in Cell Biology. ,vol. 22, pp. 124- 131 ,(2010) , 10.1016/J.CEB.2009.11.014
Subhadip Mukhopadhyay, Prashanta Kumar Panda, Niharika Sinha, Durgesh Nandini Das, Sujit Kumar Bhutia, Autophagy and apoptosis: where do they meet? Apoptosis. ,vol. 19, pp. 555- 566 ,(2014) , 10.1007/S10495-014-0967-2
Noboru Mizushima, Masaaki Komatsu, Autophagy: Renovation of Cells and Tissues Cell. ,vol. 147, pp. 728- 741 ,(2011) , 10.1016/J.CELL.2011.10.026
Jin-Woo Jeong, Cheng-Yun Jin, Cheol Park, Su Hyun Hong, Gi-Young Kim, Yong Kee Jeong, Jae-Dong Lee, Young Hyun Yoo, Yung Hyun Choi, Induction of apoptosis by cordycepin via reactive oxygen species generation in human leukemia cells. Toxicology in Vitro. ,vol. 25, pp. 817- 824 ,(2011) , 10.1016/J.TIV.2011.02.001
Wei He, Mei-fang Zhang, Jun Ye, Ting-ting Jiang, Xu Fang, Ying Song, Cordycepin induces apoptosis by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules Journal of Zhejiang University SCIENCE B. ,vol. 11, pp. 654- 660 ,(2010) , 10.1631/JZUS.B1000081