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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| Format: | Article |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-06979-2 |
| _version_ | 1818420426845454336 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T12:54:17Z |
| format | Article |
| id | doaj.art-aa5007e439df488c8463e0c4fd458bc4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T12:54:17Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-aa5007e439df488c8463e0c4fd458bc42022-12-21T23:00:37ZengNature PortfolioScientific Reports2045-23222017-07-017111110.1038/s41598-017-06979-2Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalkCun-dong Fan0Xiao-yan Fu1Zong-yong Zhang2Ming-zhi Cao3Jing-yi Sun4Ming-feng Yang5Xiao-ting Fu6Shi-jun Zhao7Lu-rong Shao8Hui-fang Zhang9Xiao-yi Yang10Bao-liang Sun11Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical UniversityKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical UniversityKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical UniversityDepartment of Neurosurgery, Huxi Hospital, Jining Medical University, ShanxianWonju Severance Christian Hospital, Yonsei University Wonju College of MedicineKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical UniversityKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical UniversityKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical UniversityKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical UniversityKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical UniversityKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical UniversityKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical UniversityAbstract 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.https://doi.org/10.1038/s41598-017-06979-2 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-06979-2 |
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