cytochrome-c-t and cepharanthine

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.

Topics: Alkaloids; Animals; Anthracenes; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Benzylisoquinolines; Carcinoma, Hepatocellular; Caspase 3; Caspases; Cell Line, Tumor; Collagen Type XI; Cytochromes c; Down-Regulation; Enzyme Activation; Enzyme Inhibitors; Humans; Liver Neoplasms; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase 9; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species