Department of Food and Nutrition, Hannam University Daedeok Valley Campus, 461-6 Jeonmin-dong, Yuseong-gu, Daejeon 305-811, Republic of Korea.
Cancer Lett. 2010 Jun 28;292(2):228-36. doi: 10.1016/j.canlet.2009.12.005. Epub 2010 Jan 18.
Effective strategies for cancer prevention and treatment can be identified by understanding the mechanism of apoptotic pathways. In this study, we investigated the regulatory mechanism of quercetin-induced apoptosis through apoptosis signal-regulating kinase (ASK)-1 and mitogen-activated protein kinase pathways. Our results showed that quercetin increased apoptotic cell death through reactive oxygen species (ROS) generation and was responsible for ASK1 activation. Increasing ASK1 activity was accompanied by p38 activation. Interestingly, AMP-activated protein kinase (AMPK) seemed to be a critical controller of quercetin-regulated ASK1/p38 activation. Blocking AMPKalpha1 activity using Compound C, a synthetic inhibitor or siRNA showed that quercetin-activated ASK1 could not stimulate p38 activity. Thus, we suggested that quercetin-exerted apoptotic effects involve ROS/AMPKalpha1/ASK1/p38 signaling pathway, and AMPKalpha1 is a necessary element for apoptotic event induced by ASK1.
通过了解凋亡途径的机制，可以确定有效的癌症预防和治疗策略。在这项研究中，我们通过凋亡信号调节激酶（ASK）-1 和丝裂原活化蛋白激酶途径研究了槲皮素诱导凋亡的调节机制。我们的结果表明，槲皮素通过活性氧（ROS）的产生增加凋亡细胞死亡，并且负责 ASK1 的激活。ASK1 活性的增加伴随着 p38 的激活。有趣的是，AMP 激活的蛋白激酶（AMPK）似乎是槲皮素调节的 ASK1/p38 激活的关键控制器。使用合成抑制剂 Compound C 或 siRNA 阻断 AMPKalpha1 活性表明，槲皮素激活的 ASK1 不能刺激 p38 活性。因此，我们认为，槲皮素发挥凋亡作用涉及 ROS/AMPKalpha1/ASK1/p38 信号通路，并且 AMPKalpha1 是 ASK1 诱导的凋亡事件所必需的。
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