Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2)
Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2)
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DOI：
10.1093/jn/136.11.2715
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发表时间：
2006-11-01
影响因子：
4.2
通讯作者：
Ramos, Sonia
中科院分区：
文献类型：
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作者：
Belen Granado-Serrano, Ana;Angeles Martin, Maria;Ramos, Sonia
膳食多酚与降低癌症等慢性疾病的风险有关，但其确切的潜在保护机制仍不清楚。本研究的目的是研究槲皮素对人肝癌细胞系 (HepG2) 细胞凋亡途径激活的影响。用槲皮素处理细胞18小时，以剂量依赖性方式诱导细胞死亡；然而，较短的处理（4 小时）对细胞活力没有影响。 HepG2 细胞与槲皮素一起孵育 18 小时，通过激活 caspase-3 和 -9（但不激活 caspase-8）诱导细胞凋亡。此外，这种类黄酮降低了 Bcl-x(L):Bcl-x(S) 比率，并增加了 Bax 向线粒体膜的易位。槲皮素处理的细胞中也出现了对主要生存信号 Akt 和细胞外调节激酶 (ERK) 的持续抑制。这些数据表明槲皮素可能通过直接激活 caspase 级联（线粒体途径）和抑制 HepG2 中的生存信号来诱导细胞凋亡。
Dietary polyphenols have been associated with the reduced risk of chronic diseases such as cancer, but the precise underlying mechanism of protection remains unclear. The aim of this study was to investigate the effect of quercetin on the activation of the apoptotic pathway in a human hepatoma cell line (HepG2). Treatment of cells for 18 h with quercetin induced cell death in a dose-dependent manner; however, a shorter treatment (4 h) had no effect on cell viability. Incubation of HepG2 cells with quercetin for 18 h induced apoptosis by the activation of caspase-3 and -9, but not caspase-8. Moreover, this flavonoid decreased the Bcl-x(L):Bcl-x(S) ratio and increased translocation of Bax to the mitochondrial membrane. A sustained inhibition of the major survival signals, Akt and extracellular regulated kinase (ERK), also occurred in quercetin-treated cells. These data suggest that quercetin may induce apoptosis by direct activation of caspase cascade (mitochondrial pathway) and by inhibiting survival signaling in HepG2.