title: Role of thioredoxin reductase 1 in dysplastic transformation of human breast epithelial cells triggered by chronic oxidative stress.
abstract: Thioredoxin reductase 1 (TrxR1) is a pivotal intracellular redox sensor and antioxidant enzyme. On the other hand, overexpression of TrxR1 is closely correlated with the initiation of various tumors including breast cancer, though the detailed mechanism remains unclear. Here we investigated the role of TrxR1 in dysplastic transformation of human breast epithelial cell line MCF-10A induced by chronic oxidative stress. Not surprisingly, sustained exposure to H2O2significantly augmented the expression and activity of TrxR1 in MCF-10A cells. The dysplastically transformed MCF-10A (MCF-10AT) cells undergoing 8-week H2O2treatment exhibited a certain degree of malignancy in tumorigenicity evaluation. Moreover, TrxR1 inhibitor ethaselen (BBSKE) could partially reverse some malignant phenotypes including epithelial to mesenchymal transition (EMT) of MCF-10AT as well as MCF-7 cells. Collectively, our results supported the considerable involvement of TrxR1 in the onset of breast cancer and BBSKE may be a promising agent against breast cancer.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, P.R. China.|Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, P.R. China.
authors.forename: Chaoran
authors.initials: C
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, P.R. China.|Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, P.R. China.|Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, P.R. China.
authors.forename: Ruoxuan
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing 100191, P.R. China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Liu
authors.affiliation: Keaise Center for Clinical Laboratory, Wuhan 430000, P.R. China.
authors.forename: Hanwei
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of pharmacy, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, P.R. China.|Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, P.R. China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, P.R. China.|Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, P.R. China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Zeng
mesh_terms: D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D005348:Fibrocystic Breast Disease / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D053552:Keratin-7 / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008875:Middle Aged; D008954:Models, Biological; D016566:Organoselenium Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D054481:Thioredoxin Reductase 1 / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: C478160:(1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone))ethane; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015820:Cadherins; D053552:Keratin-7; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D054481:Thioredoxin Reductase 1