Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K‐Akt–mTOR pathway
Abstract Glioma is the most common and aggressive primary brain tumor in adults with high morbidity and mortality. Rapid proliferation and diffuse migration are the main obstacles to successful glioma treatment. Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L., possesses a sig...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Pharmacology Research & Perspectives |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/prp2.1041 |
| _version_ | 1811165303075241984 |
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| author | Huaqing Chen Tong Zhu Xiaojie Huang Wenshuang Xu Zemin Di Yuyang Ma Min Xue Sixing Bi Yujun Shen Yongqiang Yu Yuxian Shen Lijie Feng |
| author_facet | Huaqing Chen Tong Zhu Xiaojie Huang Wenshuang Xu Zemin Di Yuyang Ma Min Xue Sixing Bi Yujun Shen Yongqiang Yu Yuxian Shen Lijie Feng |
| author_sort | Huaqing Chen |
| collection | DOAJ |
| description | Abstract Glioma is the most common and aggressive primary brain tumor in adults with high morbidity and mortality. Rapid proliferation and diffuse migration are the main obstacles to successful glioma treatment. Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L., possesses a significant antitumor role in several malignant tumors. In this study, we report that xanthatin suppressed glioma cells proliferation and induced apoptosis in a time‐ and concentration‐dependent manner, and was accompanied by autophagy inhibition displaying a significantly reduced LC3 punctate fluorescence and LC3II/I ratio, decreased level of Beclin 1, while increased accumulation of p62. Notably, treating glioma cells with xanthatin resulted in obvious activation of the PI3K‐Akt–mTOR signaling pathway, as indicated by increased mTOR and Akt phosphorylation, decreased ULK1 phosphorylation, which is important in modulating autophagy. Furthermore, xanthatin‐mediated pro‐apoptosis in glioma cells was significantly reversed by autophagy inducers (rapamycin or Torin1), or PI3K‐mTOR inhibitor NVP‐BEZ235. Taken together, these findings indicate that anti‐proliferation and pro‐apoptosis effects of xanthatin in glioma are most likely by inhibiting autophagy via activation of PI3K‐Akt–mTOR pathway, suggesting a potential therapeutic strategy against glioma. |
| first_indexed | 2024-04-10T15:35:05Z |
| format | Article |
| id | doaj.art-f56af28f2c2c47838dd0ddbbbe5d2187 |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-04-10T15:35:05Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-f56af28f2c2c47838dd0ddbbbe5d21872023-02-13T07:58:31ZengWileyPharmacology Research & Perspectives2052-17072023-02-01111n/an/a10.1002/prp2.1041Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K‐Akt–mTOR pathwayHuaqing Chen0Tong Zhu1Xiaojie Huang2Wenshuang Xu3Zemin Di4Yuyang Ma5Min Xue6Sixing Bi7Yujun Shen8Yongqiang Yu9Yuxian Shen10Lijie Feng11School of Basic Medical Sciences Anhui Medical University Hefei ChinaSchool of Basic Medical Sciences Anhui Medical University Hefei ChinaSchool of Basic Medical Sciences Anhui Medical University Hefei ChinaSchool of Basic Medical Sciences Anhui Medical University Hefei ChinaSchool of Basic Medical Sciences Anhui Medical University Hefei ChinaSchool of Basic Medical Sciences Anhui Medical University Hefei ChinaSchool of Basic Medical Sciences Anhui Medical University Hefei ChinaInstitute of Biopharmaceuticals Anhui Medical University Hefei ChinaSchool of Basic Medical Sciences Anhui Medical University Hefei ChinaThe First Affiliated Hospital of Anhui Medical University Hefei ChinaSchool of Basic Medical Sciences Anhui Medical University Hefei ChinaSchool of Basic Medical Sciences Anhui Medical University Hefei ChinaAbstract Glioma is the most common and aggressive primary brain tumor in adults with high morbidity and mortality. Rapid proliferation and diffuse migration are the main obstacles to successful glioma treatment. Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L., possesses a significant antitumor role in several malignant tumors. In this study, we report that xanthatin suppressed glioma cells proliferation and induced apoptosis in a time‐ and concentration‐dependent manner, and was accompanied by autophagy inhibition displaying a significantly reduced LC3 punctate fluorescence and LC3II/I ratio, decreased level of Beclin 1, while increased accumulation of p62. Notably, treating glioma cells with xanthatin resulted in obvious activation of the PI3K‐Akt–mTOR signaling pathway, as indicated by increased mTOR and Akt phosphorylation, decreased ULK1 phosphorylation, which is important in modulating autophagy. Furthermore, xanthatin‐mediated pro‐apoptosis in glioma cells was significantly reversed by autophagy inducers (rapamycin or Torin1), or PI3K‐mTOR inhibitor NVP‐BEZ235. Taken together, these findings indicate that anti‐proliferation and pro‐apoptosis effects of xanthatin in glioma are most likely by inhibiting autophagy via activation of PI3K‐Akt–mTOR pathway, suggesting a potential therapeutic strategy against glioma.https://doi.org/10.1002/prp2.1041autophagygliomamTORtumorigenicityxanthatin |
| spellingShingle | Huaqing Chen Tong Zhu Xiaojie Huang Wenshuang Xu Zemin Di Yuyang Ma Min Xue Sixing Bi Yujun Shen Yongqiang Yu Yuxian Shen Lijie Feng Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K‐Akt–mTOR pathway Pharmacology Research & Perspectives autophagy glioma mTOR tumorigenicity xanthatin |
| title | Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K‐Akt–mTOR pathway |
| title_full | Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K‐Akt–mTOR pathway |
| title_fullStr | Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K‐Akt–mTOR pathway |
| title_full_unstemmed | Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K‐Akt–mTOR pathway |
| title_short | Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K‐Akt–mTOR pathway |
| title_sort | xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the pi3k akt mtor pathway |
| topic | autophagy glioma mTOR tumorigenicity xanthatin |
| url | https://doi.org/10.1002/prp2.1041 |
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