Granado-Serrano Ana Belén, Angeles Martín María, Bravo Laura, Goya Luis, Ramos Sonia
Department of Metabolism and Nutrition, Instituto del Frío, Consejo Superior de Investigaciones Científicas (CSIC), José Antonio Novais 10, Ciudad Universitaria, Madrid, Spain.
Mol Nutr Food Res. 2008 Apr;52(4):457-64. doi: 10.1002/mnfr.200700203.
Quercetin, a dietary flavonoid, has been shown to possess anticarcinogenic properties, but the precise molecular mechanisms of action are not thoroughly elucidated. This study was aimed at investigating the time-course regulation effect of quercetin on survival/proliferation pathways in a human hepatoma cell line (HepG2). Quercetin induced a significant time-dependent inactivation of the major survival signaling proteins, i. e., phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B (AKT), extracellular regulated kinase (ERK), protein kinase C-alpha (PKC-alpha), in concert with a time-dependent activation of key death-related signals: c-jun amino-terminal kinase (JNK) and PKC-delta. These data suggest that quercetin exerts a tight regulation of survival/proliferation pathways that requires the integration of different signals and persists over time, being the balance of these regulatory signals what determines the fate of HepG2 cells.
槲皮素是一种膳食类黄酮,已被证明具有抗癌特性,但其确切的分子作用机制尚未完全阐明。本研究旨在探讨槲皮素对人肝癌细胞系(HepG2)存活/增殖途径的时间进程调节作用。槲皮素诱导主要存活信号蛋白即磷脂酰肌醇3激酶(PI 3激酶)/蛋白激酶B(AKT)、细胞外调节激酶(ERK)、蛋白激酶Cα(PKCα)发生显著的时间依赖性失活,同时伴随关键死亡相关信号即c-jun氨基末端激酶(JNK)和PKCδ的时间依赖性激活。这些数据表明,槲皮素对存活/增殖途径进行严格调控,这需要整合不同信号并随时间持续存在,这些调节信号的平衡决定了HepG2细胞的命运。