Dieckol from Ecklonia cava Suppresses the Migration and Invasion of HT1080 Cells by Inhibiting the Focal Adhesion Kinase Pathway Downstream of Rac1-ROS Signaling
Dieckol from Ecklonia cava Suppresses the Migration and Invasion of HT1080 Cells by Inhibiting the Focal Adhesion Kinase Pathway Downstream of Rac1-ROS Signaling
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DOI：
10.1007/s10059-012-2192-6
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发表时间：
2012-02-01
影响因子：
3.8
通讯作者：
Jeon, You Jin
中科院分区：
文献类型：
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作者：
Park, Sun Joo;Jeon, You Jin
我们先前已经从棕色的海桑（Ecklonia cava）中分离出了dieckol，一种营养多酚化合物（Lee等人，2010年a）。Dieckol显示抗肿瘤和抗氧化活性，因此对于开发针对癌症的化学预防剂和化学治疗剂具有特别的意义。然而，迪可尔发挥其抗肿瘤活性的机制知之甚少。在这里，我们表明，dieckol，来自E。cava通过清除细胞内活性氧（reactive oxygen species，ROS）抑制HT 1080细胞的迁移和侵袭。H2 O2或整合素信号介导的ROS产生增加了HT 1080细胞的迁移和侵袭，这与Rac 1活化以及粘着斑激酶（FAK）表达和磷酸化增加相关。Rac 1的激活是ROS生成所必需的。FAK的siRNA耗竭抑制Rac 1-ROS诱导的细胞迁移和侵袭。Dieckol处理减弱了细胞内ROS水平和Rac 1的活化以及FAK的表达和磷酸化。Dieckol治疗还减少FAK-Src-p130 Cas复合物的形成和MMP 2、9和13的表达。这些结果表明，Rac 1-ROS连接的级联增强迁移和HT 1080细胞的侵袭诱导表达的MMPs通过激活FAK信号通路，而dieckol下调FAK信号通过清除细胞内的ROS。这一发现为dieckol抑制人类癌症进展和转移的机制提供了新的见解。因此，我们认为，dieckol是一种潜在的治疗药物，用于癌症的治疗。
We have previously isolated dieckol, a nutrient polyphenol compound, from the brown alga, Ecklonia cava (Lee et al., 2010a). Dieckol shows both antitumor and antioxidant activity and thus is of special interest for the development of chemopreventive and chemotherapeutic agents against cancer. However, the mechanism by which dieckol exerts its antitumor activity is poorly understood. Here, we show that dieckol, derived from E. cava, inhibits migration and invasion of HT1080 cells by scavenging intracellular reactive oxygen species (ROS). H2O2 or integrin signal-mediated ROS generation increases migration and invasion of HT1080 cells, which correlates with Rac1 activation and increased expression and phosphorylation of focal adhesion kinase (FAK). Rac1 activation is required for ROS generation. Depletion of FAK by siRNA suppresses Rac1-ROS-induced cell migration and invasion. Dieckol treatment attenuated intracellular ROS levels and activation of Rac1 as well as expression and phosphorylation of FAK. Dieckol treatment also decreases complex formation of FAK-Src-p130Cas and expression of MMP2, 9, and 13. These results suggest that the Rac1-ROS-linked cascade enhances migration and invasion of HT1080 cells by inducing expression of MMPs through activation of the FAK signaling pathway, whereas dieckol downregulates FAK signaling through scavenging intracellular ROS. This finding provides new insights into the mechanisms by which dieckol is able to suppress human cancer progresssion and metastasis. Therefore, we suggest that dieckol is a potential therapeutic agent for cancer treatment.