Inhibitory effect of green tea extract and (-)-epigallocatechin-3-gallate on mammalian thioredoxin reductase and hela cell viability
文献类型：期刊论文
| 作者 | Wang, Yan1; Zhang, Huihui1; Holmgren, Arne2; Tian, Weixi1; Zhong, Liangwei1 |
| 刊名 | Oncology reports
 |
| 出版日期 | 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 |
| WOS记录号 | WOS:000261293300026 |
| 出版者 | SPANDIDOS PUBL LTD |
| URI标识 | http://www.irgrid.ac.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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来源：中国科学院大学
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