2 '-epi-2 '-O-Acetylthevetin B extracted from seeds of Cerbera manghas L. induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells

doi:10.1016/j.cbi.2009.10.012

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	2 '-epi-2 '-O-Acetylthevetin B extracted from seeds of Cerbera manghas L. induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells
	Feng, Bo 2; Guo, Yue-Wei1 ; Huang, Cai-Guo 2; Li, Liang1 ; Chen, Ruo-Hua 3; Jiao, Bing-Hua 2
刊名	CHEMICO-BIOLOGICAL INTERACTIONS
	2010-01-05
卷号	183 期号:1 页码:142-153
关键词	2 '-epi-2 '-O-Acetylthevetin B (GHSC-74) Cell cycle arrest Mitochondrial membrane potential (Delta psi(m)) Apoptosis-inducing factor (AIF) Reactive oxygen species (ROS) Caspase Apoptosis
ISSN号	0009-2797
DOI	10.1016/j.cbi.2009.10.012
文献子类	Article
英文摘要	2'-epi-2'-O-Acetylthevetin B (GHSC-74) is a cardiac glycoside isolated from the seeds of Cerbera manghas L We have demonstrated that GHSC-74 reduced the viability of HepG2 cells in a time-and dose-dependent manner. The present study was designed to explore cellular mechanisms whereby GHSC-74 led to cell cycle arrest and apoptosis in HepG2 cells. Cell cycle flow cytometry demonstrated that HepG2 cells treated with GHSC-74 (4 mu M) resulted in S and G2 phase arrest in a time-dependent manner, as confirmed by mitotic index analysis. G2 phase arrest was accompanied with down-regulation of CDC2 and Cyclin B1 protein. Furthermore, GHSC-74-induced apoptotic killing, as demonstrated by DNA fragmentation, DAPI staining, and flow cytometric detection of sub-G1 DNA content in HepG2 cells. GHSC-74 treatment resulted in a significant increase in reactive oxygen species, activation of caspase-9, dissipation of mitochondrial membrane potential, and translocation of apoptosis-inducing factor (AIF) from the mitochondrion to the nucleus in HepG2 cells. Nevertheless, after GHSC-74 exposure, no significant Fas and FasL up-regulation was observed in HepG2 cells by flow cytometry. In addition, treatment with antioxidant N-acetyl-L-cysteine (NAC) and broad-spectrum caspase inhibitor z-VAD-fmk partially prevented apoptosis but did not abrogate GHSC-74-induced nuclear translocation of AIR In conclusion, we have demonstrated that GHSC-74 inhibited growth of HepG2 cells by inducing S and G2 phase arrest of the cell cycle and by triggering apoptosis via mitochondrial disruption including both caspase-dependent and -independent pathways, and ROS generation. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
资助项目	Ministry of Science and Technology of China[2006AAD9Z447]
WOS关键词	NF-KAPPA-B ; ALPHA-INDUCED APOPTOSIS ; NECROSIS-FACTOR-ALPHA ; HUMAN LEUKEMIA-CELLS ; NITROGEN-MUSTARD ; DEATH ; MITOCHONDRIA ; ACTIVATION ; ROS ; KINASE
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000273864800016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278998]
专题	天然药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室上海药物代谢研究中心
通讯作者	Huang, Cai-Guo
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Second Mil Med Univ, Dept Biochem & Mol Biol, Shanghai 200433, Peoples R China; 3.Changhai Hosp, Shanghai 200433, Peoples R China
推荐引用方式 GB/T 7714	Feng, Bo,Guo, Yue-Wei,Huang, Cai-Guo,et al. 2 '-epi-2 '-O-Acetylthevetin B extracted from seeds of Cerbera manghas L. induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells[J]. CHEMICO-BIOLOGICAL INTERACTIONS,2010,183(1):142-153.
APA	Feng, Bo,Guo, Yue-Wei,Huang, Cai-Guo,Li, Liang,Chen, Ruo-Hua,&Jiao, Bing-Hua.(2010).2 '-epi-2 '-O-Acetylthevetin B extracted from seeds of Cerbera manghas L. induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells.CHEMICO-BIOLOGICAL INTERACTIONS,183(1),142-153.
MLA	Feng, Bo,et al."2 '-epi-2 '-O-Acetylthevetin B extracted from seeds of Cerbera manghas L. induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells".CHEMICO-BIOLOGICAL INTERACTIONS 183.1(2010):142-153.