2. Academic Validation
  3. Tenacissoside H repressed the progression of glioblastoma by inhibiting the PI3K/Akt/mTOR signaling pathway

Tenacissoside H repressed the progression of glioblastoma by inhibiting the PI3K/Akt/mTOR signaling pathway

  • Eur J Pharmacol. 2024 Feb 7:968:176401. doi: 10.1016/j.ejphar.2024.176401.
Jianhong Dong 1,  Yiming Qian 1,  Wei Zhang 2,  Jiayun Xu 2,  Lipei Wang 3,  Ziwei Fan 4,  Mengxian Jia 4,  Lijia Wei 2,  Hui Yang 2,  Xuan Luo 2,  Yongjie Wang 2,  Yuanyuan Jiang 2,  Zhihui Huang 5,  Ying Wang 6
Affiliations

Affiliations

  • 1 Department of Clinical Research Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310053, Zhejiang, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China.
  • 2 School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China.
  • 3 School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, 310030, Zhejiang, China.
  • 4 Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
  • 5 School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China. Electronic address: huang0069@hznu.edu.cn.
  • 6 Department of Clinical Research Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310053, Zhejiang, China. Electronic address: nancywangying@163.com.
PMID: 38331340 DOI: 10.1016/j.ejphar.2024.176401
Abstract

Glioblastoma (GBM) is one of the most common intracranial primary malignancies with the highest mortality rate, and there is a lack of effective treatments. In this study, we examined the anti-GBM activity of Tenacissoside H (TH), an active component isolated from the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Wight & Arn (MT), and investigated the potential mechanism. Firstly, we found that TH decreased the viability of GBM cells by inducing cell cycle arrest and Apoptosis, and inhibited the migration of GBM cells. Furthermore, combined with the Gene Expression Omnibus database (GEO) and network pharmacology as well as molecular docking, TH was shown to inhibit GBM progression by directly regulating the PI3K/Akt/mTOR pathway, which was further validated in vitro. In addition, the selective PI3K agonist 740 y-p partially restored the inhibitory effects of TH on GBM cells. Finally, TH inhibited GBM progression in an orthotopic transplantation model by inactivating the PI3K/Akt/mTOR pathway in vivo. Conclusively, our results suggest that TH represses GBM progression by inhibiting the PI3K/Akt/mTOR signaling pathway in vitro and in vivo, and provides new insight for the treatment of GBM patients.

Keywords

Apoptosis; Glioblastoma; Migration; Proliferation; Tenacissoside H; mTOR.

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