Li Jianliang, Li Jingchen, Guo Erkun
The Second Hospital of Hebei Medical University, No.215 Heping West Road, Shijiazhuang, Hebei, 050000, China.
Anticancer Agents Med Chem. 2025;25(14):1041-1048. doi: 10.2174/0118715206332048241126095207.
Our study aimed to explore the effects of quercetin on glioma stem cells in patients with brain tumors.
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.
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.
In conclusion, quercetin inhibits glioma cell growth by activating p16-INK4 gene expression through epigenetic regulation.
我们的研究旨在探讨槲皮素对脑肿瘤患者神经胶质瘤干细胞的影响。
用槲皮素处理人胶质母细胞瘤细胞系U373MG或神经胶质瘤干细胞系。使用细胞计数试剂盒8检测法测定细胞活力。使用膜联蛋白V试剂测定细胞凋亡。采用蛋白质免疫印迹法和定量聚合酶链反应检测细胞周期蛋白依赖性激酶抑制剂2A（p16INK4a）的蛋白质和mRNA水平。采用染色质免疫沉淀分析确定有无槲皮素时p16-INK4基因座上H3K27me3的富集情况。
槲皮素处理可抑制U373MG细胞的活力并诱导其凋亡。此外，槲皮素处理在高浓度时可抑制来自脑肿瘤样本的四种神经胶质瘤干细胞系（G3、G10、G15和G17）的细胞活力，而对另外两种神经胶质瘤干细胞系（G9和G21）无明显影响。槲皮素处理可提高神经胶质瘤干细胞系中p16-INK4的mRNA和蛋白质水平。对潜在机制的研究表明，槲皮素处理可降低p16-INK4基因座上H3K27me3（一种对DNA包装蛋白组蛋白H3的表观遗传修饰）的水平。
总之，槲皮素通过表观遗传调控激活p16-INK4基因表达来抑制神经胶质瘤细胞生长。
