Academic Journal
Daurisoline suppress glioma progression by inhibiting autophagy through PI3K/AKT/mTOR pathway and increases TMZ sensitivity.
| Τίτλος: | Daurisoline suppress glioma progression by inhibiting autophagy through PI3K/AKT/mTOR pathway and increases TMZ sensitivity. |
|---|---|
| Συγγραφείς: | Yin HT; Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, PR China; College of Pharmacy, Guizhou Medical University, Guiyang, Guizhou Province, PR China., Hui-Lu; Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, PR China; College of Pharmacy, Guizhou Medical University, Guiyang, Guizhou Province, PR China., Yang JH; Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, PR China; College of Pharmacy, Guizhou Medical University, Guiyang, Guizhou Province, PR China. Electronic address: 2391490225@qq.com., Li Q; Centre of Clinical Trials, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, PR China., Li M; Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, PR China; College of Pharmacy, Guizhou Medical University, Guiyang, Guizhou Province, PR China. Electronic address: xlm3@yeah.net., Zhao QQ; Clinical Research Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, PR China., Wen ZP; Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, PR China; College of Pharmacy, Guizhou Medical University, Guiyang, Guizhou Province, PR China. Electronic address: wenzhipeng@gmc.edu.cn. |
| Πηγή: | Biochemical pharmacology [Biochem Pharmacol] 2024 May; Vol. 223, pp. 116113. Date of Electronic Publication: 2024 Mar 07. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Elsevier Science Original Publication: Oxford, New York [etc.] Paragamon Press. |
| Ιατρικοί όροι (MeSH): | Brain Neoplasms*/metabolism , Glioma*/pathology , Benzylisoquinolines*, Temozolomide/pharmacology ; Temozolomide/therapeutic use ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Mice ; Animals ; Humans ; Mice, Nude ; Autophagy ; Cell Line, Tumor ; Apoptosis ; Drug Resistance, Neoplasm |
| Περίληψη: | Glioma is one of the most common primary malignant tumors of the central nervous system. Temozolomide (TMZ) is the only effective chemotherapeutic agent, but it easily develops resistance and has unsatisfactory efficacy. Consequently, there is an urgent need to develop safe and effective compounds for glioma treatment. The cytotoxicity of 30 candidate compounds to glioma cells was detected by the CCK-8 assay. Daurisoline (DAS) was selected for further investigation due to its potent anti-glioma effects. Our study revealed that DAS induced glioma cell apoptosis through increasing caspase-3/6/9 activity. DAS significantly inhibited the proliferation of glioma cells by inducing G1-phase cell cycle arrest. Meanwhile, DAS remarkably suppressed the migration and invasion of glioma cells by regulating epithelial-mesenchymal transition. Mechanistically, our results revealed that DAS impaired the autophagic flux of glioma cells at a late stage by mediating the PI3K/AKT/mTOR pathway. DAS could inhibit TMZ-induced autophagy and then significantly promote TMZ chemosensitivity. Nude mice xenograft model revealed that DAS could restrain glioma proliferation and promote TMZ chemosensitivity. Thus, DAS is a potential anti-glioma drug that can improve glioma sensitivity to TMZ and provide a new therapeutic strategy for glioma in chemoresistance. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Apoptosis; Autophagy; Daurisoline; Glioma; Temozolomide |
| Substance Nomenclature: | YF1K15M17Y (Temozolomide) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) 70553-76-3 (daurisoline) EC 2.7.11.1 (TOR Serine-Threonine Kinases) 0 (Benzylisoquinolines) |
| Entry Date(s): | Date Created: 20240309 Date Completed: 20240422 Latest Revision: 20240910 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.bcp.2024.116113 |
| PMID: | 38460907 |
| Βάση Δεδομένων: | MEDLINE |
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