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Cepharanthine triggers apoptosis in a human hepatocellular carcinoma cell line (HuH‐7) through the activation of JNK1/2 and the downregulation of Akt
Author(s) -
Biswas Kamal Krishna,
Tancharon Salunya,
Sarker Krishna Pada,
Kawahara Ko-ichi,
Hashiguchi Teruto,
Maruyama Ikuro
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.12.048
Subject(s) - downregulation and upregulation , apoptosis , hepatocellular carcinoma , protein kinase b , hepatic carcinoma , cancer research , cell culture , pi3k/akt/mtor pathway , chemistry , microbiology and biotechnology , biology , biochemistry , gene , genetics
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.