title: Cordycepin induces autophagy-mediated c-FLIPL degradation and leads to apoptosis in human non-small cell lung cancer cells.
abstract: 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.
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, China.
authors.forename: Xinghui
authors.initials: X
authors.lastname: Yu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, China.
authors.forename: Jianya
authors.initials: J
authors.lastname: Ling
authors.affiliation: The Department of Otolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Xianfang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Guo
authors.affiliation: The Thoracic Surgery Department of West China Hospital, West China Medical School of Sichuan University, Chengdu, China.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, China.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Su
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5 / Q000235:genetics / Q000378:metabolism; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053181:Caspase 8 / Q000378:metabolism; D049109:Cell Proliferation; D003839:Deoxyadenosines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D059748:Proteolysis; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: C502778:ATG5 protein, human; D000970:Antineoplastic Agents; D000071187:Autophagy-Related Protein 5; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D003839:Deoxyadenosines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D058570:TOR Serine-Threonine Kinases; C505530:CASP8 protein, human; D053181:Caspase 8; C058120:cordycepin
keywords: apoptosis; autophagy; c-FLIP; cordycepin