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Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk.
Fan, Cun-Dong; Fu, Xiao-Yan; Zhang, Zong-Yong; Cao, Ming-Zhi; Sun, Jing-Yi; Yang, Ming-Feng; Fu, Xiao-Ting; Zhao, Shi-Jun; Shao, Lu-Rong; Zhang, Hui-Fang; Yang, Xiao-Yi; Sun, Bao-Liang.
Afiliação
  • Fan CD; Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
  • Fu XY; Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
  • Zhang ZY; Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
  • Cao MZ; Department of Neurosurgery, Huxi Hospital, Jining Medical University, Shanxian, 274300, Shandong, China.
  • Sun JY; Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Gangwon, 220-701, Korea.
  • Yang MF; Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
  • Fu XT; Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
  • Zhao SJ; Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
  • Shao LR; Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
  • Zhang HF; Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
  • Yang XY; Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China. xyyang@tsmc.edu.cn.
  • Sun BL; Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China. tblsun66@163.com.
Sci Rep ; 7(1): 6465, 2017 07 25.
Article em En | MEDLINE | ID: mdl-28743999
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Selenocisteína / Tiorredoxina Redutase 1 / Glioma / Antineoplásicos Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Selenocisteína / Tiorredoxina Redutase 1 / Glioma / Antineoplásicos Idioma: En Ano de publicação: 2017 Tipo de documento: Article