Celastrol Suppresses SHH-MB Growth via ROS-Induced Stress: Evidence From In Vitro and In Vivo Studies.
Bohong Wang1, Tao Xu1, Lisheng Yu1
1Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China.
Phytotherapy Research : PTR
|August 22, 2025
Summary
Celastrol effectively inhibits Sonic Hedgehog medulloblastoma (SHH-MB) by inducing cell death and reducing tumor growth. This natural compound shows promise as a new therapeutic strategy for SHH-MB, warranting further clinical investigation.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Medulloblastoma (MB), particularly the Sonic Hedgehog (SHH) subtype, presents significant therapeutic challenges due to its aggressive nature.
- Limited effective treatment options exist for SHH-MB, necessitating the exploration of novel therapeutic agents.
- Celastrol, a compound from Tripterygium wilfordii, exhibits known anticancer properties.
Purpose of the Study:
- To investigate the inhibitory effects of celastrol on Sonic Hedgehog medulloblastoma (SHH-MB) cells.
- To elucidate the underlying mechanisms and signaling pathways involved in celastrol's anti-SHH-MB activity.
- To evaluate celastrol's efficacy in both in vitro and in vivo models of SHH-MB.
Main Methods:
- Cell proliferation, migration, invasion, and apoptosis were assessed using CCK-8, Ki-67, colony formation, scratch wound, and transwell assays.
- An SHH-MB mouse xenograft model was utilized for in vivo efficacy evaluation.
- Flow cytometry, Western blotting, molecular reverse virtual screening, GEO database analysis, and transcriptomic analysis were employed to explore mechanisms, including ROS levels, apoptosis-related proteins, PI3K-AKT, TGFB2, and the CXCL12/NF-κB signaling axis.
Main Results:
- Celastrol significantly inhibited SHH-MB cell proliferation, migration, invasion, and colony formation in vitro and in vivo.
- Celastrol induced apoptosis in SHH-MB cells, partly mediated by increased intracellular reactive oxygen species (ROS) levels.
- Transcriptomic analysis indicated that celastrol downregulates TGF-beta2 and CXCL12 mRNA expression, potentially via the NF-κB signaling pathway.
Conclusions:
- Celastrol exhibits significant antitumor activity against SHH-MB by inducing ROS-mediated apoptosis and suppressing proliferation, migration, and invasion.
- The therapeutic effects of celastrol may involve the suppression of the CXCL12/NF-κB signaling axis.
- Celastrol represents a promising therapeutic strategy for SHH-MB, meriting further clinical investigation.
