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Juglone induces ferroptosis in glioblastoma cells by inhibiting the Nrf2-GPX4 axis through the phosphorylation of p38MAPK
- Source :
- Chinese Medicine, Vol 19, Iss 1, Pp 1-16 (2024)
- Publication Year :
- 2024
- Publisher :
- BMC, 2024.
-
Abstract
- Abstract Background Ferroptosis, a non-apoptotic form of cell death induced by accumulation of free iron ions and lipid peroxidation, its importance for cancer treatment is gradually being recognized. Research on the anti-cancer mechanism of juglone is accumulating. However, the specific mechanism by which it directs glioblastoma (GBM) to death is unknown. Methods We used in vitro and in vivo experiments to explore the anti-GBM effect generated by juglone through the ferroptosis pathway. Results Juglone mainly causes cell death by inducing ferroptosis. Mechanistically, juglone can significantly activate the phosphorylation of p38MAPK. According to transcriptome sequencing and protein interaction analysis, the Nrf2-GPX4 signaling pathway is identified as the primary pathway through which juglone mediates ferroptosis. In vitro and in vivo experiments further verified that juglone induces the ferroptosis of GBM by activating the phosphorylation of p38MAPK and negatively regulating the Nrf2-GPX4 signaling pathway. Conclusion Juglone induces ferroptosis and inhibits the growth of GBM by targeting the Nrf2/Gpx4 signaling pathway and thus holds promise as a novel ferroptosis inducer or anti-GBM drug.
- Subjects :
- Juglone
Glioblastoma
Ferroptosis
p38MAPK
Nrf2
Other systems of medicine
RZ201-999
Subjects
Details
- Language :
- English
- ISSN :
- 17498546
- Volume :
- 19
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Chinese Medicine
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.fd4e93570d446d38932f1510a4f4c59
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13020-024-00920-2