Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk

Abstract Thioredoxin reductase (TrxR) as a selenium (Se)-containing antioxidase plays key role in regulating intracellular redox status. Selenocystine (SeC) a natural available Se-containing amino acid showed novel anticancer potential through triggering oxidative damage-mediated apoptosis. However,...

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Autores principales:	Cun-dong Fan, Xiao-yan Fu, Zong-yong Zhang, Ming-zhi Cao, Jing-yi Sun, Ming-feng Yang, Xiao-ting Fu, Shi-jun Zhao, Lu-rong Shao, Hui-fang Zhang, Xiao-yi Yang, Bao-liang Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa5007e439df488c8463e0c4fd458bc4
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spelling	oai:doaj.org-article:aa5007e439df488c8463e0c4fd458bc42021-12-02T11:52:15ZSelenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk10.1038/s41598-017-06979-22045-2322https://doaj.org/article/aa5007e439df488c8463e0c4fd458bc42017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06979-2https://doaj.org/toc/2045-2322Abstract Thioredoxin reductase (TrxR) as a selenium (Se)-containing antioxidase plays key role in regulating intracellular redox status. Selenocystine (SeC) a natural available Se-containing amino acid showed novel anticancer potential through triggering oxidative damage-mediated apoptosis. However, whether TrxR-mediated oxidative damage was involved in SeC-induced apoptosis in human glioma cells has not been elucidated yet. Herein, SeC-induced human glioma cell apoptosis was detected in vitro, accompanied by PARP cleavage, caspases activation and DNA fragmentation. Mechanically, SeC caused mitochondrial dysfunction and imbalance of Bcl-2 family expression. SeC treatment also triggered ROS-mediated DNA damage and disturbed the MAPKs and AKT pathways. However, inhibition of ROS overproduction effectively attenuated SeC-induced oxidative damage and apoptosis, and normalized the expression of MAPKs and AKT pathways, indicating the significance of ROS in SeC-induced apoptosis. Importantly, U251 human glioma xenograft growth in nude mice was significantly inhibited in vivo. Further investigation revealed that SeC-induced oxidative damage was achieved by TrxR1-targeted inhibition in vitro and in vivo. Our findings validated the potential of SeC to inhibit human glioma growth by oxidative damage-mediated apoptosis through triggering TrxR1-targeted inhibition.Cun-dong FanXiao-yan FuZong-yong ZhangMing-zhi CaoJing-yi SunMing-feng YangXiao-ting FuShi-jun ZhaoLu-rong ShaoHui-fang ZhangXiao-yi YangBao-liang SunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cun-dong Fan Xiao-yan Fu Zong-yong Zhang Ming-zhi Cao Jing-yi Sun Ming-feng Yang Xiao-ting Fu Shi-jun Zhao Lu-rong Shao Hui-fang Zhang Xiao-yi Yang Bao-liang Sun Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk
description	Abstract Thioredoxin reductase (TrxR) as a selenium (Se)-containing antioxidase plays key role in regulating intracellular redox status. Selenocystine (SeC) a natural available Se-containing amino acid showed novel anticancer potential through triggering oxidative damage-mediated apoptosis. However, whether TrxR-mediated oxidative damage was involved in SeC-induced apoptosis in human glioma cells has not been elucidated yet. Herein, SeC-induced human glioma cell apoptosis was detected in vitro, accompanied by PARP cleavage, caspases activation and DNA fragmentation. Mechanically, SeC caused mitochondrial dysfunction and imbalance of Bcl-2 family expression. SeC treatment also triggered ROS-mediated DNA damage and disturbed the MAPKs and AKT pathways. However, inhibition of ROS overproduction effectively attenuated SeC-induced oxidative damage and apoptosis, and normalized the expression of MAPKs and AKT pathways, indicating the significance of ROS in SeC-induced apoptosis. Importantly, U251 human glioma xenograft growth in nude mice was significantly inhibited in vivo. Further investigation revealed that SeC-induced oxidative damage was achieved by TrxR1-targeted inhibition in vitro and in vivo. Our findings validated the potential of SeC to inhibit human glioma growth by oxidative damage-mediated apoptosis through triggering TrxR1-targeted inhibition.
format	article
author	Cun-dong Fan Xiao-yan Fu Zong-yong Zhang Ming-zhi Cao Jing-yi Sun Ming-feng Yang Xiao-ting Fu Shi-jun Zhao Lu-rong Shao Hui-fang Zhang Xiao-yi Yang Bao-liang Sun
author_facet	Cun-dong Fan Xiao-yan Fu Zong-yong Zhang Ming-zhi Cao Jing-yi Sun Ming-feng Yang Xiao-ting Fu Shi-jun Zhao Lu-rong Shao Hui-fang Zhang Xiao-yi Yang Bao-liang Sun
author_sort	Cun-dong Fan
title	Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk
title_short	Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk
title_full	Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk
title_fullStr	Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk
title_full_unstemmed	Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk
title_sort	selenocysteine induces apoptosis in human glioma cells: evidence for trxr1-targeted inhibition and signaling crosstalk
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/aa5007e439df488c8463e0c4fd458bc4
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Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk

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