Instituto del Frío-Instituto de Ciencia y Tecnología de Alimentos y Nutrición, Madrid, Spain.
Nutr Cancer. 2010;62(3):390-401. doi: 10.1080/01635580903441196.
Quercetin, a dietary flavonoid, has been shown to possess anticarcinogenic properties, but the precise molecular mechanisms of action are not thoroughly elucidated. The aim of this study was to investigate the regulatory effect of quercetin (50 microM) on two main transcription factors (NF-kappa B and AP-1) related to survival/proliferation pathways in a human hepatoma cell line (HepG2) over time. Quercetin induced a significant time-dependent inactivation of the NF-kappa B pathway consistent with a downregulation of the NF-kappa B binding activity (from 15 min onward). These features were in concert with a time-dependent activation (starting at 15 min and maintained up to 18 h) of the AP-1/JNK pathway, which played an important role in the control of the cell death induced by the flavonoid and contributed to the regulation of survival/proliferation (AKT, ERK) and death (caspase-3, p38, unbalance of Bcl-2 proapoptotic and antiapoptotic proteins) signals. These data suggest that NF-kappa B and AP-1 play a main role in the tight regulation of survival/proliferation pathways exerted by quercetin and that the sustained JNK/AP-1 activation and inhibition of NF-kappa B provoked by the flavonoid induced HepG2 death.
槲皮素是一种膳食类黄酮，已被证明具有抗癌特性，但确切的作用机制尚未完全阐明。本研究旨在探讨槲皮素（50μM）对与人肝癌细胞系（HepG2）中与生存/增殖途径相关的两个主要转录因子（NF-κB 和 AP-1）的时间依赖性调节作用。槲皮素诱导 NF-κB 途径的显著时间依赖性失活，与 NF-κB 结合活性的下调一致（从 15 分钟开始）。这些特征与 AP-1/JNK 途径的时间依赖性激活（从 15 分钟开始并持续至 18 小时）一致，该途径在控制黄酮诱导的细胞死亡中起着重要作用，并有助于调节生存/增殖（AKT、ERK）和死亡（caspase-3、p38、Bcl-2 促凋亡和抗凋亡蛋白的失衡）信号。这些数据表明，NF-κB 和 AP-1 在槲皮素对生存/增殖途径的严格调控中起主要作用，黄酮诱导的 HepG2 死亡引发的 JNK/AP-1 持续激活和 NF-κB 抑制。
