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	Inhibition of mammalian thioredoxin reductase by black tea and its constituents: implications for anticancer actions
	Du, Yatao1; Wu, Yunfei1; Cao, Xueli2; Cui, Wei3; Zhang, Huihui1; Tian, Weixi1; Ji, Mingjuan; Holmgren, Arne4; Zhong, Liangwei1
刊名	Biochimie
	2009-03-01
卷号	91期号:3页码:434-444
关键词	Thioredoxin reductase Black tea Theaflavins Anticancer Pro-oxidant
ISSN号	0300-9084
DOI	10.1016/j.biochi.2008.11.005
通讯作者	Zhong, liangwei(liazho@gucas.ac.cn)
英文摘要	Black tea is recently reported to have anti-carcinogenic effects through pro-oxidant property, but the underlying mechanisms remain unclear. mammalian cytosolic thioredoxin reductase (trxr1) is well-known for its anti-oxidation activity. in this study, we found that black tea extract (bte) and theaflavins (tfs), the major black tea polyphenols, inhibited the purified trxr1 with ic(50) 44 mu g/ml and 21 +/- 5 mu g/ml, respectively. kinetics of tfs exhibited a mixed type of competitive and non-competitive inhibition, with k(is) 4 +/- 1 mu g/ml and k(ii) 26 +/- 5 mu g/ml against coenzyme nadph, and with k(is) 12 +/- 3 mu g/ml and k(ii) 27 +/- 5 mu g/ml against substrate dtnb. in addition, tfs inhibited trxr1 in a time-dependent manner. in an equilibrium step, a reversible trxr1-tfs complex (e * i) forms, which is followed by a slow irreversible first-order inactivation step. rate constant of the inactivation was 0.7 min(-1), and dissociation constant of e * i was 51.9 mu g/ml. treatment of nadph-reduced trxr1 with tfs decreased 5-(iodoacetamido) fluorescein incorporation, a fluorescent thiol-reactive reagent, suggesting that sec/cys residue(s) in the active site may be involved in the binding of tfs. the inhibitory capacity of tfs depends on their structure. among the tfs tested, gallated forms had strong inhibitory effects. the interactions between tfs and trxr1 were investigated by molecular docking, which revealed important features of the binding mechanism of theaflavins. an inhibitory effect of bte on viability of hela cells was observed with ic(50) 29 mu g/ml. at 33 mu g/ml of bte, trxr1 activity in hela cells was decreased by 73% at 22 h after bte treatment. tfs inhibited cell viability with ic(50) 10 +/- 4 mu g/ml for hela cells and with ic(50) 20 +/- 5 mu g/ml for eahy926 cells. the cell susceptibility to tfs was inversely correlated to cellular levels of trxr1. the inhibitory actions of tfs on trxr1 may be an important mechanism of their anti-cancer properties. (c) 2008 elsevier masson sas. all rights reserved.
WOS关键词	PROTEIN-1 TRANSCRIPTION FACTOR ; (-)-EPIGALLOCATECHIN GALLATE ; MOLECULAR-MECHANISM ; ESCHERICHIA-COLI ; OXIDATIVE STRESS ; CANCER CELLS ; THEAFLAVINS ; APOPTOSIS ; CHROMATOGRAPHY ; POLYPHENOLS
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000264433400014
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2397240
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.Beijing Technol & Business Univ, Beijing Key Lab Plant Resource Res & Dev, Beijing, Peoples R China 3.Chinese Acad Sci, Grad Univ, Coll Chem & Chem Engn, Beijing 100049, Peoples R China 4.Karolinska Inst, Dept Med Biochem & Biophys, Med Nobel Inst Biochem, SE-17177 Stockholm, Sweden
推荐引用方式 GB/T 7714	Du, Yatao,Wu, Yunfei,Cao, Xueli,et al. Inhibition of mammalian thioredoxin reductase by black tea and its constituents: implications for anticancer actions[J]. Biochimie,2009,91(3):434-444.
APA	Du, Yatao.,Wu, Yunfei.,Cao, Xueli.,Cui, Wei.,Zhang, Huihui.,...&Zhong, Liangwei.(2009).Inhibition of mammalian thioredoxin reductase by black tea and its constituents: implications for anticancer actions.Biochimie,91(3),434-444.
MLA	Du, Yatao,et al."Inhibition of mammalian thioredoxin reductase by black tea and its constituents: implications for anticancer actions".Biochimie 91.3(2009):434-444.

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