Quercetin Suppresses Glioma Stem Cells via Activating p16-INK4 Gene Expression through Epigenetic Regulation.

IF 2.6 4区 医学 Q3 CHEMISTRY, MEDICINAL
Jianliang Li, Jingchen Li, Erkun Guo
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引用次数: 0

Abstract

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.

槲皮素通过表观遗传调控激活p16-INK4基因表达抑制胶质瘤干细胞
目的:探讨槲皮素对脑肿瘤患者胶质瘤干细胞的影响。方法:用槲皮素处理人胶质瘤细胞株U373MG或胶质瘤干细胞。采用细胞计数试剂盒8测定细胞活力。Annexin-V试剂检测细胞凋亡。Western blotting和qPCR检测环无关激酶抑制剂2A (p16INK4a)的蛋白和mRNA水平。采用染色质免疫沉淀法测定在加或不加槲皮素的情况下p16-INK4位点上H3K27me3的富集情况。结果:槲皮素抑制U373MG细胞活力,诱导细胞凋亡。此外,槲皮素在高浓度下抑制了脑肿瘤样本中4种胶质瘤干细胞系(G3、G10、G15和G17)的细胞活力,而对另外2种胶质瘤干细胞系(G9和G21)无明显影响。槲皮素处理可提高胶质瘤干细胞p16- INK4 mRNA和蛋白水平。潜在机制的研究表明,槲皮素处理降低了p16-INK4位点的H3K27me3 (DNA包装蛋白H3的表观遗传修饰)水平。结论:槲皮素通过表观遗传调控激活p16-INK4基因表达,从而抑制胶质瘤细胞生长。
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来源期刊
Anti-cancer agents in medicinal chemistry
Anti-cancer agents in medicinal chemistry ONCOLOGY-CHEMISTRY, MEDICINAL
CiteScore
5.10
自引率
3.60%
发文量
323
审稿时长
4-8 weeks
期刊介绍: Formerly: Current Medicinal Chemistry - Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents. Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication. Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.
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