Celastrol Suppresses SHH‐MB Growth via ROS‐Induced Stress: Evidence From In Vitro and In Vivo Studies
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2025
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| author | Bohong Wang Tao Xu Lisheng Yu Chenjie Qiu Jing Xu Xiangmao Zhao Chao Xu Feng Tan Hansong Sheng Nu Zhang Shangyu Xu |
| author_facet | Bohong Wang Tao Xu Lisheng Yu Chenjie Qiu Jing Xu Xiangmao Zhao Chao Xu Feng Tan Hansong Sheng Nu Zhang Shangyu Xu Bohong Wang Tao Xu Lisheng Yu Chenjie Qiu Jing Xu Xiangmao Zhao Chao Xu Feng Tan Hansong Sheng Nu Zhang Shangyu Xu |
| collection | Wiley Open Access |
| contents | Celastrol Suppresses SHH‐MB Growth via ROS‐Induced Stress: Evidence From In Vitro and In Vivo Studies Bohong Wang Tao Xu Lisheng Yu Chenjie Qiu Jing Xu Xiangmao Zhao Chao Xu Feng Tan Hansong Sheng Nu Zhang Shangyu Xu Phytotherapy Research ABSTRACTCelastrol, a bioactive compound derived from the traditional Chinese herb Tripterygium wilfordii, has demonstrated various pharmacological properties, including anticancer effects. Medulloblastoma (MB), particularly the Sonic Hedgehog (SHH) subtype, remains a challenge due to its aggressive nature and limited therapeutic options. This study aims to investigate the inhibitory effects of celastrol on Sonic Hedgehog medulloblastoma (SHH‐MB) cells in vitro and in vivo, focusing on its underlying mechanisms and signaling pathways. The effects of celastrol on cell proliferation were evaluated using the Cell Counting Kit‐8 (CCK‐8) assay, Ki‐67 immunofluorescence staining, and colony formation assay. The scratch wound healing assay and transwell invasion assay were used to explore its effects on cell migration and invasion. An SHH‐MB mouse xenograft model was constructed to assess the anti‐cancer effect of celastrol. Flow cytometry was employed to detect the apoptotic effect and intracellular reactive oxygen species (ROS) levels, and Western blotting was used to analyze apoptosis‐related proteins. In terms of mechanism exploration, through molecular reverse virtual screening, analysis of the medulloblastoma Gene Expression Omnibus (GEO) database, and transcriptomic analysis, it was speculated that celastrol might affect the PI3K‐AKT pathway through TGFB2. Finally, Western blotting was used to verify the results related to this pathway. Celastrol significantly inhibited SHH‐MB cell proliferation and induced apoptosis in both in vitro and in vivo models. Celastrol increased intracellular ROS levels, contributing to apoptosis, and effectively suppressed SHH‐MB cell migration, invasion, and colony formation. Transcriptomic analysis revealed that celastrol downregulates TGF‐beta2 and CXCL12 mRNA expression, potentially through the NF‐κB signaling pathway, further supporting its antiproliferative effects. Celastrol demonstrates significant antitumor activity against SHH‐MB by inducing ROS‐mediated apoptosis and inhibiting proliferation, migration, and invasion. Its effects may involve suppression of the CXCL12/NF‐κB signaling axis, providing a promising therapeutic strategy for SHH‐MB treatment. Further research is warranted to explore its clinical applications. 10.1002/ptr.70077 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.70077 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_70077 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Celastrol Suppresses SHH‐MB Growth via ROS‐Induced Stress: Evidence From In Vitro and In Vivo Studies Bohong Wang Tao Xu Lisheng Yu Chenjie Qiu Jing Xu Xiangmao Zhao Chao Xu Feng Tan Hansong Sheng Nu Zhang Shangyu Xu Phytotherapy Research Celastrol Suppresses SHH‐MB Growth via ROS‐Induced Stress: Evidence From In Vitro and In Vivo Studies Bohong Wang Tao Xu Lisheng Yu Chenjie Qiu Jing Xu Xiangmao Zhao Chao Xu Feng Tan Hansong Sheng Nu Zhang Shangyu Xu Phytotherapy Research ABSTRACTCelastrol, a bioactive compound derived from the traditional Chinese herb Tripterygium wilfordii, has demonstrated various pharmacological properties, including anticancer effects. Medulloblastoma (MB), particularly the Sonic Hedgehog (SHH) subtype, remains a challenge due to its aggressive nature and limited therapeutic options. This study aims to investigate the inhibitory effects of celastrol on Sonic Hedgehog medulloblastoma (SHH‐MB) cells in vitro and in vivo, focusing on its underlying mechanisms and signaling pathways. The effects of celastrol on cell proliferation were evaluated using the Cell Counting Kit‐8 (CCK‐8) assay, Ki‐67 immunofluorescence staining, and colony formation assay. The scratch wound healing assay and transwell invasion assay were used to explore its effects on cell migration and invasion. An SHH‐MB mouse xenograft model was constructed to assess the anti‐cancer effect of celastrol. Flow cytometry was employed to detect the apoptotic effect and intracellular reactive oxygen species (ROS) levels, and Western blotting was used to analyze apoptosis‐related proteins. In terms of mechanism exploration, through molecular reverse virtual screening, analysis of the medulloblastoma Gene Expression Omnibus (GEO) database, and transcriptomic analysis, it was speculated that celastrol might affect the PI3K‐AKT pathway through TGFB2. Finally, Western blotting was used to verify the results related to this pathway. Celastrol significantly inhibited SHH‐MB cell proliferation and induced apoptosis in both in vitro and in vivo models. Celastrol increased intracellular ROS levels, contributing to apoptosis, and effectively suppressed SHH‐MB cell migration, invasion, and colony formation. Transcriptomic analysis revealed that celastrol downregulates TGF‐beta2 and CXCL12 mRNA expression, potentially through the NF‐κB signaling pathway, further supporting its antiproliferative effects. Celastrol demonstrates significant antitumor activity against SHH‐MB by inducing ROS‐mediated apoptosis and inhibiting proliferation, migration, and invasion. Its effects may involve suppression of the CXCL12/NF‐κB signaling axis, providing a promising therapeutic strategy for SHH‐MB treatment. Further research is warranted to explore its clinical applications. 10.1002/ptr.70077 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Celastrol Suppresses SHH‐MB Growth via ROS‐Induced Stress: Evidence From In Vitro and In Vivo Studies |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.70077 |