Quercetin Modulates NF-κB and AP-1/JNK Pathways to Induce Cell Death in Human Hepatoma Cells
Quercetin Modulates NF-κB and AP-1/JNK Pathways to Induce Cell Death in Human Hepatoma Cells
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DOI：
10.1080/01635580903441196
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发表时间：
2010-01-01
影响因子：
2.9
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
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。本研究的目的是调查槲皮素（50 μ M）的调节作用，对两个主要的转录因子（NF-κ B B和AP-1）相关的生存/增殖途径在人肝癌细胞系（HepG 2）随着时间的推移。槲皮素诱导NF-κ B途径的显著时间依赖性失活，与NF-κ B结合活性的下调一致（从15 min开始）。这些特征与AP-1/JNK通路的时间依赖性激活（从15 min开始并维持长达18 h）一致，AP-1/JNK通路在控制类黄酮诱导的细胞死亡中起重要作用，并有助于调节存活/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-κ B和AP-1在槲皮素对存活/增殖途径的严格调节中起主要作用，并且类黄酮引起的持续JNK/AP-1活化和NF-κ B抑制诱导HepG 2死亡。
Quercetin, a dietary flavonoid, has been shown to possess anti-carcinogenic 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 mu M) 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.