Back to Search
Start Over
5-Demethylnobiletin mediates cell cycle arrest and apoptosis via the ERK1/2/AKT/STAT3 signaling pathways in glioblastoma cells
- Source :
- Frontiers in Oncology, Vol 13 (2023)
- Publication Year :
- 2023
- Publisher :
- Frontiers Media S.A., 2023.
-
Abstract
- 5-Demethylnobiletin is the active ingredient in citrus polymethoxyflavones that could inhibit the proliferation of several tumor cells. However, the anti-tumor effect of 5-Demethylnobiletin on glioblastoma and the underlying molecular mechanisms are remains unknown. In our study, 5-Demethylnobiletin markedly inhibited the viability, migration and invasion of glioblastoma U87-MG, A172 and U251 cells. Further research revealed that 5-Demethylnobiletin induces cell cycle arrest at the G0/G1 phase in glioblastoma cells by downregulating Cyclin D1 and CDK6 expression levels. Furthermore, 5-Demethylnobiletin significantly induced glioblastoma cells apoptosis by upregulating the protein levels of Bax and downregulating the protein level of Bcl-2, subsequently increasing the expression of cleaved caspase-3 and cleaved caspase-9. Mechanically, 5-Demethylnobiletin trigged G0/G1 phase arrest and apoptosis by inhibiting the ERK1/2, AKT and STAT3 signaling pathway. Furthermore, 5-Demethylnobiletin inhibition of U87-MG cell growth was reproducible in vivo model. Therefore, 5-Demethylnobiletin is a promising bioactive agent that might be used as glioblastoma treatment drug.
Details
- Language :
- English
- ISSN :
- 2234943X
- Volume :
- 13
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Oncology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.b741caa98d454188a74bfa10bb50caf8
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fonc.2023.1143664