Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells
Objective Aloperine (ALO), an alkaloid isolated from the leaves of Sophora alopecuroides, has been suggested to exhibit anti-inflammatory and anti-tumor properties and is traditionally used to treat various human diseases, including cancer. However, limited information is available about the mechani...
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PeerJ Inc.
2019-09-01
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| Online Access: | https://peerj.com/articles/7652.pdf |
| _version_ | 1797418939009990656 |
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| author | Zhijie Xu Xiang Wang Xi Chen Shuangshuang Zeng Long Qian Jie Wei Zhicheng Gong Yuanliang Yan |
| author_facet | Zhijie Xu Xiang Wang Xi Chen Shuangshuang Zeng Long Qian Jie Wei Zhicheng Gong Yuanliang Yan |
| author_sort | Zhijie Xu |
| collection | DOAJ |
| description | Objective Aloperine (ALO), an alkaloid isolated from the leaves of Sophora alopecuroides, has been suggested to exhibit anti-inflammatory and anti-tumor properties and is traditionally used to treat various human diseases, including cancer. However, limited information is available about the mechanisms that determine the anti-tumor activities of ALO. Methods Herein, through comprehensive bioinformatics methods and in vitro functional analyses, we evaluated the detailed anti-tumor mechanisms of ALO. Results Using the databases Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine and PubChem Project, we identified the potential targets of ALO. A protein–protein interaction network was constructed to determine the relationship among these probable targets. Functional enrichment analysis revealed that ALO is potentially involved in the induction of apoptosis. In addition, molecular docking demonstrated that ALO expectedly docks into the active pocket of the Bcl2 protein, suggesting Bcl2 as a direct target of ALO. Moreover, western blot and qPCR analysis showed that ALO downregulated Bcl2 expression in human glioma cell lines, SK-N-AS and U118. Using flow cytometry methods, we further confirmed that ALO significantly promotes apoptosis in SK-N-AS and U118 cell lines, similar to the effect induced by ABT-737, a well-known Bcl2 inhibitor. In addition, Bcl-2 overexpression could rescue ALO-induced Bcl-2 inhibition and suppress pro-apoptotic effects in glioma cells. Conclusion Taken together, these findings suggest that the natural agent ALO effectively enhances apoptosis by acting as a potential Bcl2 inhibitor in human glioma cells. |
| first_indexed | 2024-03-09T06:40:12Z |
| format | Article |
| id | doaj.art-63294fc73e444908a0a25812ae3bec87 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:40:12Z |
| publishDate | 2019-09-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-63294fc73e444908a0a25812ae3bec872023-12-03T10:51:37ZengPeerJ Inc.PeerJ2167-83592019-09-017e765210.7717/peerj.7652Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cellsZhijie Xu0Xiang Wang1Xi Chen2Shuangshuang Zeng3Long Qian4Jie Wei5Zhicheng Gong6Yuanliang Yan7Department of Pathology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaObjective Aloperine (ALO), an alkaloid isolated from the leaves of Sophora alopecuroides, has been suggested to exhibit anti-inflammatory and anti-tumor properties and is traditionally used to treat various human diseases, including cancer. However, limited information is available about the mechanisms that determine the anti-tumor activities of ALO. Methods Herein, through comprehensive bioinformatics methods and in vitro functional analyses, we evaluated the detailed anti-tumor mechanisms of ALO. Results Using the databases Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine and PubChem Project, we identified the potential targets of ALO. A protein–protein interaction network was constructed to determine the relationship among these probable targets. Functional enrichment analysis revealed that ALO is potentially involved in the induction of apoptosis. In addition, molecular docking demonstrated that ALO expectedly docks into the active pocket of the Bcl2 protein, suggesting Bcl2 as a direct target of ALO. Moreover, western blot and qPCR analysis showed that ALO downregulated Bcl2 expression in human glioma cell lines, SK-N-AS and U118. Using flow cytometry methods, we further confirmed that ALO significantly promotes apoptosis in SK-N-AS and U118 cell lines, similar to the effect induced by ABT-737, a well-known Bcl2 inhibitor. In addition, Bcl-2 overexpression could rescue ALO-induced Bcl-2 inhibition and suppress pro-apoptotic effects in glioma cells. Conclusion Taken together, these findings suggest that the natural agent ALO effectively enhances apoptosis by acting as a potential Bcl2 inhibitor in human glioma cells.https://peerj.com/articles/7652.pdfBcl2 inhibitorApoptosisAloperineGlioma |
| spellingShingle | Zhijie Xu Xiang Wang Xi Chen Shuangshuang Zeng Long Qian Jie Wei Zhicheng Gong Yuanliang Yan Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells PeerJ Bcl2 inhibitor Apoptosis Aloperine Glioma |
| title | Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells |
| title_full | Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells |
| title_fullStr | Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells |
| title_full_unstemmed | Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells |
| title_short | Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells |
| title_sort | identification of aloperine as an anti apoptotic bcl2 protein inhibitor in glioma cells |
| topic | Bcl2 inhibitor Apoptosis Aloperine Glioma |
| url | https://peerj.com/articles/7652.pdf |
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