Cordycepol C Induces Caspase-Independent Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells
Sun, Yi-sheng1,2; Lv, Long-xian1; Zhao, Zhao1; He, Xian1; You, Lu3; Liu, Ji-kai4; Li, Yong-quan1
2014-04-01
发表期刊BIOLOGICAL & PHARMACEUTICAL BULLETIN
ISSN0918-6158
卷号37期号:4页码:608-617
摘要Cordycepol C, a novel sesquiterpene isolated from the cultured mycelia of Cordyceps ophioglossoides, contains a hydroperoxy group and is cytotoxic to HepG2 cells. So far, no sesquiterpenes have been found in the genus Cordyceps and it would be interesting to investigate the antitumor efficacy as well as the mechanism of action of this unusual sesquiterpene. In this study, we showed that cordycepol C induced apoptosis of the HepG2 cells without affecting the normal liver cell line L-02. Cordycepol C caused poly(ADP-ribose) polymerase-1 (PARP-1) cleavage and triggered the loss of mitochondrial membrane potential (Delta psi(m)) in HepG2 cells in a time- and dose-dependent manner, resulting in the nuclear translocation of apoptosis-inducing factor (AIF) and endonuclease G (Endo G). We also found that cordycepol C induced the expression of Bax protein, followed by its translocation from the cytosol to mitochondria in both wild type and p53 knockdown HepG2 cells. However, cordycepol C could not cause cleavages of procaspase-3, -8, and -9. Caspase activities were not increased and Z-VAD-fmk, a caspase inhibitor, could not prevent the apoptosis induced by cordycepol C. These findings indicate that cordycepol C induces caspase-independent apoptosis in HepG2 cells through a p53-independent and Bax-mediated mitochondrial pathway, leading to the nuclear translocation of AIF and Endo G. Our study provides the molecular mechanism by which cordycepol C induces apoptosis in hepatocellular carcinoma cells and indicates the potential use of cordycepol C as an antitumor agent.
关键词Cordycepol c Apoptosis Bax Protein Apoptosis-inducing Factor Endonuclease g
资助信息National High Technology Research and Development Program of China [2007AA021506]; Natural Science Foundation of Zhejiang Province, China [R207609]
收录类别SCI
语种英语
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/18043
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Zhejiang Univ, Coll Life Sci, Hangzhou 310058, Zhejiang, Peoples R China
2.Zhejiang Prov Ctr Dis Control & Prevent, Hangzhou 310051, Zhejiang, Peoples R China
3.Huangyan Tradit Chinese Med Hosp, Dept Orthoped, Taizhou 318000, Peoples R China
4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650204, Peoples R China
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Sun, Yi-sheng,Lv, Long-xian,Zhao, Zhao,et al. Cordycepol C Induces Caspase-Independent Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells[J]. BIOLOGICAL & PHARMACEUTICAL BULLETIN,2014,37(4):608-617.
APA Sun, Yi-sheng.,Lv, Long-xian.,Zhao, Zhao.,He, Xian.,You, Lu.,...&Li, Yong-quan.(2014).Cordycepol C Induces Caspase-Independent Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells.BIOLOGICAL & PHARMACEUTICAL BULLETIN,37(4),608-617.
MLA Sun, Yi-sheng,et al."Cordycepol C Induces Caspase-Independent Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells".BIOLOGICAL & PHARMACEUTICAL BULLETIN 37.4(2014):608-617.
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