Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway

Lee,Hye  Hyeon; Jeong,Jin-Woo; Lee,Jun   Hyuk; Kim,Gi-Young; Cheong,Jaehun; Jeong,Yong  Kee; Yoo,Young  Hyun; Choi,Yung  Hyun

doi:10.3892/or.2013.2589

Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway

Authors:
- Hye Hyeon Lee
- Jin-Woo Jeong
- Jun Hyuk Lee
- Gi-Young Kim
- Jaehun Cheong
- Yong Kee Jeong
- Young Hyun Yoo
- Yung Hyun Choi
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Affiliations: Department of Biotechnology and Medi-Farm Industrialization Research Center, Dong-A University, Busan 604‑714, Republic of Korea, Center for Core Research Facilities, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, Republic of Korea, Biotechnology Examination Division, Chemistry and Biotechnology Examination Bureau, Korean Intellectual Property Office, Daejeon 302-701, Republic of Korea, Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea, Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea, Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea, Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea
Published online on: July 4, 2013 https://doi.org/10.3892/or.2013.2589
Pages: 1257-1264

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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.

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