Cepharanthine triggers apoptosis in a human hepatocellular carcinoma cell line (HuH-7) through the activation of JNK1/2 and the downregulation of Akt |
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Authors: | Biswas Kamal Krishna Tancharoen Salunya Tancharon Salunya Sarker Krishna Pada Kawahara Ko-ichi Hashiguchi Teruto Maruyama Ikuro |
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Affiliation: | Department of Laboratory and Vascular Medicine, Faculty of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. |
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Abstract: | Cepharanthine (CEP), a biscoclaurine alkaloid, has been reported to induce cell death, however, the molecular mechanism of this phenomenon remains unclear. We herein report that CEP induced apoptosis in HuH-7 cells through nuclear fragmentation, DNA ladder formation, cytochrome c release, caspase-3 activation and poly-(ADP-ribose)-polymerase cleavage. CEP triggered the generation of reactive oxygen intermediates, the activation of mitogen activated protein kinase (MAPK) p38, JNK1/2 and p44/42, and the downregulation of protein kinase B/Akt. Antioxidants and SP600125, an inhibitor of JNK1/2, but not inhibitors of p38 MAPK and MEK1/2, significantly prevented cell death, thus implying that reactive oxygen species and JNK1/2 play crucial roles in the CEP-induced apoptosis of HuH-7 cells. |
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Keywords: | CEP, cepharanthine JNK, c-Jun N-terminal kinase MAPK, mitogen activated protein kinase ROS, reactive oxygen species NAC, N-acetyl cysteine PARP, poly-(ADP-ribose)-polymerase |
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