title: Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway.
abstract: Resistance to tumor necrosis factor-related apoptosis‑inducing ligand (TRAIL)-induced apoptosis has been reported in various cancer cells. Cordycepin, a specific polyadenylation inhibitor, is the main functional component in Cordyceps militaris, which possesses many pharmacological activities including antitumor and anti-inflammation. In the present study, we demonstrated that treatment of cordycepin sensitized TRAIL-resistant Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis as evidenced by formation of apoptotic bodies, chromatin condensation and accumulation of cells in the sub-G1 phase. The induction of apoptosis following co-treatment with cordycepin and TRAIL in Hep3B cells appeared to be correlated with modulation of Bcl-2 family protein expression and activation of the caspase cascade, which resulted in the cleavage of poly(ADP-ribose) polymerase and β-catenin. In addition, cordycepin treatment also inhibited activation of c-Jun N-terminal kinase (JNK). Pretreatment with SP600125, a JNK inhibitor, resulted in a significantly increased sub-G1 population and caspase activity in cordycepin plus TRAIL-mediated apoptosis. Taken together, these results indicate that JNK acts as a key regulator of apoptosis in response to combined treatment with cordycepin and TRAIL in human hepatocellular carcinoma Hep3B cells.
authors.affiliation: Department of Biotechnology and Medi-Farm Industrialization Research Center, Dong-A University, Busan 604‑714, Republic of Korea.
authors.forename: Hye Hyeon
authors.initials: HH
authors.lastname: Lee
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Jeong
authors.forename: Jun Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Jaehun
authors.initials: J
authors.lastname: Cheong
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Jeong
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases; C058120:cordycepin