Apoptosis induced by a new member of saponin family is mediated through caspase-8-dependent cleavage of Bcl-2

	Apoptosis induced by a new member of saponin family is mediated through caspase-8-dependent cleavage of Bcl-2
	Zhu, JB; Xiong, L; Yu, B; Wu, JR
刊名	MOLECULAR PHARMACOLOGY
	2005
卷号	68 期号:6 页码:1831-1838
通讯作者	Wu, JR (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Lab Proteom, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,wujr@sibs.ac.cn
英文摘要	OSW-1 is a new member of cholestane saponin family, which is cytotoxic against several types of malignant cells. We reported herein that OSW-1 induced apoptosis of mammalian cells in a concentration- and time-dependent manner. The drug-induced apoptosis was mediated through the mitochondrial pathway, involving the cleavage of Bcl-2. This drug-induced Bcl-2 cleavage in Chinese hamster ovary (CHO) cells could be suppressed either by dominant-negative caspase-8 or by a caspase-8 inhibitor, suggesting that the Bcl- 2 cleavage is dependent on caspase-8. In contrast, the Bcl- 2 cleavage was independent of caspase-3 activity. The inhibition of caspase-8 activity also resulted in the reduction of apoptotic cells, indicating that Bcl-2 cleavage induced by caspase-8 promotes the progression of apoptosis. The involvement of the caspase-8 activity in the processes of the OSW-1-induced apoptosis was further examined by using caspase-8-deficient Jurkat T cells. It was found that the caspase-8-deficient cells were resistant to OSW-1-induced Bcl-2 cleavage or apoptosis. Furthermore, the small subunit of caspase-8 was found to interact with Bcl-2 as determined by yeast two-hybrid and coimmunoprecipitation assays. Overexpression of caspase-8 small subunit reduced the cleavage of Bcl-2 and inhibited the apoptosis induced by OSW-1. Taken together, these results demonstrate that OSW-1 is capable of inducing apoptosis in mammalian cells, in which the caspase-8-dependent cleavage of Bcl-2 plays an important role.
学科主题	Pharmacology & Pharmacy
类目[WOS]	Pharmacology & Pharmacy
关键词[WOS]	PROGRAMMED CELL-DEATH ; ORNITHOGALUM-SAUNDERSIAE ; CHOLESTANE GLYCOSIDES ; MITOCHONDRIAL RELEASE ; PROTEIN-KINASE ; CYTOCHROME-C ; IN-VITRO ; FAS ; INHIBITION ; ACTIVATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000233340200034
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1924]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhu, JB,Xiong, L,Yu, B,et al. Apoptosis induced by a new member of saponin family is mediated through caspase-8-dependent cleavage of Bcl-2[J]. MOLECULAR PHARMACOLOGY,2005,68(6):1831-1838.
APA	Zhu, JB,Xiong, L,Yu, B,&Wu, JR.(2005).Apoptosis induced by a new member of saponin family is mediated through caspase-8-dependent cleavage of Bcl-2.MOLECULAR PHARMACOLOGY,68(6),1831-1838.
MLA	Zhu, JB,et al."Apoptosis induced by a new member of saponin family is mediated through caspase-8-dependent cleavage of Bcl-2".MOLECULAR PHARMACOLOGY 68.6(2005):1831-1838.