Quercetin Suppresses Glioma Stem Cells via Activating p16-INK4 Gene Expression through Epigenetic Regulation
Jianliang Li1, Jingchen Li1, Erkun Guo1
1The Second Hospital of Hebei Medical University, No.215 Heping West Road, Shijiazhuang, Hebei, 050000, China.
Objectives:
Our study aimed to explore the effects of quercetin on glioma stem cells in patients with brain tumors.
Methods:
Human glioblastoma cell line, U373MG, or glioma stem cell lines, were treated with quercetin. Cell viability was determined by using the cell counting kit 8 assays. Cell apoptosis was determined by using the Annexin- V reagent. Western blotting and qPCR were used to detect the protein and mRNA levels of cyclindependent kinase inhibitor 2A (p16INK4a). Chromatin immunoprecipitation analysis was used to determine the enrichment of H3K27me3 on the p16-INK4 locus with or without quercetin.
Results:
Treatment with quercetin inhibited cell viability and induced cell apoptosis in U373MG cells. Moreover, treatment with quercetin inhibited the cell viability of four glioma stem cell lines (G3, G10, G15, and G17) from brain tumor samples at high concentrations while having no obvious effects for the other two glioma stem cell lines (G9 and G21). Treatment with quercetin increased the mRNA and protein levels of p16- INK4 in glioma stem cell lines. The study of the underlying mechanism revealed that treatment with quercetin reduced H3K27me3 (an epigenetic modification to the DNA packaging protein histone H3) levels at the p16-INK4 locus.
Conclusions:
In conclusion, quercetin inhibits glioma cell growth by activating p16-INK4 gene expression through epigenetic regulation.
Insights
Quercetin, a natural compound, inhibits glioma cell growth by activating the p16-INK4 gene. This occurs through epigenetic regulation, offering a potential therapeutic avenue for brain tumors.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Glioblastoma is an aggressive brain tumor with limited treatment options.
- Glioma stem cells (GSCs) are implicated in tumor recurrence and resistance to therapy.
- Quercetin is a flavonoid with potential anti-cancer properties.
Purpose of the Study:
- To investigate the effects of quercetin on glioma stem cells.
- To elucidate the molecular mechanisms underlying quercetin's action on GSCs.
Main Methods:
- Treatment of glioblastoma and glioma stem cell lines with quercetin.
- Assessment of cell viability and apoptosis.
- Analysis of p16INK4a protein and mRNA expression via Western blotting and qPCR.
- Chromatin immunoprecipitation to evaluate H3K27me3 enrichment at the p16-INK4 locus.
Main Results:
- Quercetin inhibited viability and induced apoptosis in U373MG cells.
- Quercetin suppressed viability in some GSC lines (G3, G10, G15, G17) at high concentrations.
- Quercetin increased p16INK4a expression and reduced H3K27me3 at the p16-INK4 locus in GSCs.
Conclusions:
- Quercetin exhibits anti-proliferative and pro-apoptotic effects on glioma cells.
- Quercetin activates p16INK4a gene expression via epigenetic modification (reduced H3K27me3).
- Epigenetic regulation by quercetin presents a potential therapeutic strategy for brain tumors.
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