Cepharanthine triggers apoptosis in a human hepatocellular carcinoma cell line (HuH-7) through the activation of JNK1/2 and the downregulation of Akt.
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.
Biswas
Kamal Krishna
KK
Department of Laboratory and Vascular Medicine, Faculty of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Tancharoen
Salunya
S
Tancharon
Salunya
S
Sarker
Krishna Pada
KP
Kawahara
Ko-ichi
K
Hashiguchi
Teruto
T
Maruyama
Ikuro
I
D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D000873:Anthracenes / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D044182:Benzylisoquinolines; D006528:Carcinoma, Hepatocellular; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D024161:Collagen Type XI / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D052117:Benzodioxoles
D000470:Alkaloids; D000873:Anthracenes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; D053148:Caspase 3; D020169:Caspases; D024161:Collagen Type XI; D045304:Cytochromes c; D004791:Enzyme Inhibitors; D048055:Mitogen-Activated Protein Kinase 8; D048056:Mitogen-Activated Protein Kinase 9; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; C499319:COL11A2 protein, human; C432165:pyrazolanthrone; C006947:cepharanthine; D052117:Benzodioxoles; C505407:CASP3 protein, human