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5-Demethylnobiletin mediates cell cycle arrest and apoptosis via the ERK1/2/AKT/STAT3 signaling pathways in glioblastoma cells

Authors :
Xuehua Zhang
Leilei Zhao
Jinlong Xiao
Yudi Wang
Yunmeng Li
Chaoqun Zhu
He Zhang
Yurui Zhang
Xiao Zhu
Yucui Dong
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