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	Inhibitory effect of green tea extract and (-)-epigallocatechin-3-gallate on mammalian thioredoxin reductase and hela cell viability
	Wang, Yan1; Zhang, Huihui1; Holmgren, Arne2; Tian, Weixi1; Zhong, Liangwei1
刊名	Oncology reports
	2008-12-01
卷号	20期号:6页码:1479-1487
关键词	Thioredoxin reductase Green tea polyphenols Anticancer (-)-epigallocatechin-3-gallate Selenoprotein
ISSN号	1021-335X
DOI	10.3892/or_00000169
通讯作者	Zhong, liangwei(liazho@gucas.ac.cn)
英文摘要	Mammalian cytosolic thioredoxin reductase (trxr1) is an attractive target for developing cancer chemo-preventive agents since its inhibition is associated with a reduced growth of cancer cells. however, the known inhibitors of this enzyme mostly have a toxic effect oil human health. we report on a non-toxic inhibitor, green tea. trxr1 was found to be inhibited by green tea extracts (gte) with an ic(50) value of 256 mu g/ml. catechins, the major components of gte, showed various inhibitory effects, in which (-)-epigallocatechin-3gallate (egcg) exhibited a stronger inhibition than any other catechins tested. the inhibition of trxr1 by egcg was close to competitive (k(i) = 64 mu m) with substrate dtnb and was non-competitive (k(i) = 92 mu m) with co-enzyme nadph. the preincubation of trxr1 with egcg led to irreversible enzyme inactivation in a time-dependent manner, which was highly effective in the presence of nadph. the inactivation included, in equilibrium step used to form a reversible trxrl-egcg complex (ei) (dissociation constant k(i)* = 43 mu m), and an isomerization step used to form an irreversible complex (e*i) (rate constant k(3) = 4.8 x 10(-3) s(-1)). we have identified thiol/selenol groups in the active site as reactive sites that mediated trxr1 inhibition by egcg. when cultured hela cells were treated with gte or egcg for 22-24 h, trxr1 activity in cell extracts was significantly inhibited, accompanied by a reduction of cell viability in a concentration-dependent manner (ic(50) = 40 mu g/ml for gte and 107 mu m for egcg). the inactivation of trxr1 by gte/egcg is most likely linked to a reduction of hela cell viability.
WOS关键词	REDUCES LIPID HYDROPEROXIDES ; GLUTATHIONE-REDUCTASE ; GLUTAREDOXIN SYSTEMS ; HEALTHY-INDIVIDUALS ; MOLECULAR TARGET ; CANCER-THERAPY ; RAT-LIVER ; SELENOCYSTEINE ; EXPRESSION ; SUBSTRATE
WOS研究方向	Oncology
WOS类目	Oncology
语种	英语
出版者	SPANDIDOS PUBL LTD
WOS记录号	WOS:000261293300026
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2393192
专题	中国科学院大学
通讯作者	Zhong, Liangwei
作者单位	1.Chinese Acad Sci, Grad Univ, Coll Life Sci, Beijing 100049, Peoples R China 2.Karolinska Inst, Dept Med Biochem & Biophys, Med Nobel Inst Biochem, SE-17177 Stockholm, Sweden
推荐引用方式 GB/T 7714	Wang, Yan,Zhang, Huihui,Holmgren, Arne,et al. Inhibitory effect of green tea extract and (-)-epigallocatechin-3-gallate on mammalian thioredoxin reductase and hela cell viability[J]. Oncology reports,2008,20(6):1479-1487.
APA	Wang, Yan,Zhang, Huihui,Holmgren, Arne,Tian, Weixi,&Zhong, Liangwei.(2008).Inhibitory effect of green tea extract and (-)-epigallocatechin-3-gallate on mammalian thioredoxin reductase and hela cell viability.Oncology reports,20(6),1479-1487.
MLA	Wang, Yan,et al."Inhibitory effect of green tea extract and (-)-epigallocatechin-3-gallate on mammalian thioredoxin reductase and hela cell viability".Oncology reports 20.6(2008):1479-1487.

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