Induction apoptosis of luteolin in human hepatoma HepG2 cells involving mitochondria translocation of Bax/Bak and activation of JNK
- 作者：Lee ; Herng-Jiun ; Wang ; Chau-Jong ; Kuo ; Hsing-Chun ; Chou ; Fen-Pi ; Jean ; Lian-Fwu ; Tseng ; Tsui-Hwa
- 关键词：CPP32 ; cysteine protease 32 kDa proenzyme ; DMSO ; dimethyl sulfoxide ; JNK ; c-Jun NH2-terminal kinase ; p38 MAPK ; p38 mitogen-activated protein kinase ; MTT ; (3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyl tetrazolium bromide ; PARP ; poly (ADP-ribose) po
- 刊名：Toxicology and Applied Pharmacology
- 出版年：2005
- 期刊代码：58_0041008x
- 类别：pha
- 出版时间：March 1, 2005
- 卷：203
- 期：2
- 页码：124-131
- 文件大小：608 K
摘要
Since hepatocellular carcinoma remains a major challenging clinical problem in many parts of the world including Eastern Asia and Southern Africa, it is imperative to develop more effective chemopreventive and chemotherapy agents. Herein, we present an investigation regarding the anticancer potential of luteolin, a natural flavonoid, and the mechanism of its action in human hepatoma HepG2 cells. Using DNA fragmentation assay and nuclear staining assay, it showed that luteolin induced apoptosis of HepG2 cells. Luteolin induced the cytosolic release of cytochrome c and activated CPP32. We found that Bax and Bak translocated to mitochondria apparently, whereas Fas ligand (FasL) was unchanged after a treatment with luteolin for 3 h. In addition, it showed that c-Jun NH2-terminal kinase (JNK) was activated after the treatment of luteolin for 3芒芒芒12 h. Further investigation showed that a specific JNK inhibitor, SP600125, reduced the activation of CPP 32, the mitochondrial translocation of Bax, as well as the cytosolic release of cytochrome c that induced by luteolin. Finally, the apoptosis induced by luteolin was suppressed by a pretreatment with SP600125 via evaluating annexin V-FITC binding assay. These data suggest that luteolin induced apoptosis via mechanisms involving mitochondria translocation of Bax/Bak and activation of JNK.