Cepharanthine triggers apoptosis in a human hepatocellular carcinoma cell line (HuH-7) through the activation of JNK1/2 and the downregulation of Akt
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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DOI：
10.1016/j.febslet.2005.12.048
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发表时间：
2006-01-23
期刊：
影响因子：
3.5
通讯作者：
Maruyama, I
中科院分区：
文献类型：
--
作者：
Biswas, KK;Tancharon, S;Maruyama, I
Cepharanthine （CEP）是一种双氯螯合生物碱，已被报道可诱导细胞死亡，但其分子机制尚不清楚。我们在此报道CEP通过核断裂、DNA阶梯形成、细胞色素c释放、caspase-3激活和聚（adp -核糖）聚合酶裂解诱导HuH-7细胞凋亡。CEP触发活性氧中间体的生成，激活丝裂原活化蛋白激酶（MAPK） p38、JNK1/2和p44/42，下调蛋白激酶B/Akt。抗氧化剂和JNK1/2抑制剂SP600125（而非p38 MAPK和MEK1/2抑制剂）显著阻止细胞死亡，这表明活性氧和JNK1/2在cep诱导的HuH-7细胞凋亡中起关键作用。(c) 2005年欧洲生化学会联合会。Elsevier B.V.版权所有。
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. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.