title: Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma.
abstract: Forkhead transcription factor (Foxo3a) is a downstream effector of JNK-induced tumor suppression. However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JNK phosphorylation (p-JNK) and subsequent Foxo3a translocation into the nucleus, resulting in the upregulation of Bax protein expression. Furthermore, we found that CAV1 overexpression upregulated p-JNK, whereas CAV1 siRNA downregulated p-JNK. Additionally, SP600125, a specific JNK inhibitor, significantly increased Foxo3a phosphorylation, which downregulated Foxo3a translocation into the nucleus, indicating that CAV1 mediates JNK regulation of Foxo3a. Foxo3a siRNA downregulated Bax protein and attenuated A549 apoptosis, indicating that the CAV1-mediated JNK/Foxo3a pathway induces the apoptosis of A549 lung cancer cells. Cordycepin significantly decreased tumor volume in nude mice. Taken together, these results indicate that cordycepin promotes CAV1 upregulation to enhance JNK/Foxo3a signaling pathway activation, inducing apoptosis in lung cancer cells, and support its potential as a therapeutic agent for lung cancer.
authors.affiliation: Department of Sasang Constitutional Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors.forename: Jong Cheon
authors.initials: JC
authors.lastname: Joo
authors.affiliation: College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Jung Hoo
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.
authors.forename: Eunbi
authors.initials: E
authors.lastname: Jo
authors.affiliation: Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.
authors.forename: Young-Rang
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA.
authors.forename: Dae Joon
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.
authors.forename: Kyung-Bok
authors.initials: KB
authors.lastname: Lee
authors.affiliation: Department of Sasang Constitutional Medicine, Woosuk University, Wanju, Jeonbuk, 55338, Republic of Korea.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.
authors.forename: Ik-Soon
authors.initials: IS
authors.lastname: Jang
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003839:Deoxyadenosines / Q000494:pharmacology*; D000071316:Forkhead Box Protein O3 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000873:Anthracenes; D051242:Caveolin 1; D003839:Deoxyadenosines; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; C058120:cordycepin
keywords: CAV1; Foxo3a; JNK; apoptosis; cordycepin