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Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway
- Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway
- Lee, HH[Lee, Hye Hyeon]; Jeong, JW[Jeong, Jin-Woo]; Lee, JH[Lee, Jun Hyuk]; Kim, GY[Kim, Gi-Young]; Cheong, J[Cheong, Jaehun]; Jeong, YK[Jeong, Yong Kee]; Yoo, YH[Yoo, Young Hyun]; Choi, YH[Choi, Yung Hyun]
- DGIST Authors
- Jeong, JW[Jeong, Jin-Woo]
- Issue Date
- Oncology Reports, 30(3), 1257-1264
- Article Type
- Anthra[1,9 CD]Pyrazol 6(2H) One; Antineoplastic Activity; Antineoplastic Agents; Apoptosis; Beta Catenin; Blotting, Western; C-Jun N-Terminal Kinase; Cancer Cell Culture; Carcinoma, Hepatocellular; Caspase; Caspases; Cell Cycle G1 Phase; Cell Infiltration; Cell Proliferation; Chromatin Condensation; Concentration Response; Controlled Study; Cordycepin; Deoxyadenosines; Drug Sensitivity; Drug Targeting; Enzyme Inactivation; Flow Cytometry; Hep3B Cells; Human; Human Cell; Humans; JNK Mitogen-Activated Protein Kinases; Liver Cell Carcinoma; Liver Neoplasms; Membrane Potential, Mitochondrial; Nicotinamide Adenine Dinucleotide Adenosine Diphosphate Ribosyltransferase; Priority Journal; Protein BCL 2; Protein Cleavage; Protein Expression; Protein Function; Protein Protein Interaction; Real-Time Polymerase Chain Reaction; Reverse Transcriptase-Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Stress Activated Protein Kinase; TNF-Related Apoptosis-Inducing Ligand; TRAIL; Tumor Cells, Cultured; Tumor Necrosis Factor Related Apoptosis Inducing Ligand
- 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.
- Spandidos Publications
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