骨桥蛋白
蛋白激酶B
A549电池
肌动蛋白解聚因子
岩石1
板层
癌症研究
细胞迁移
癌细胞
细胞生物学
焦点粘着
Rho相关蛋白激酶
细胞
化学
生物
信号转导
癌症
肌动蛋白细胞骨架
免疫学
生物化学
罗亚
细胞骨架
遗传学
作者
Chi Gu Kang,Hyo‐Jeong Lee,Sung Hoon Kim,Eun-Ok Lee
标识
DOI:10.1021/acs.jnatprod.5b00796
摘要
Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths in the United States and Korea. We have previously demonstrated that osteopontin (OPN) induces cell invasion through inactivating cofilin. Inactivation of cofilin is mediated by the FAK/AKT/Rho-associated kinase (ROCK) pathway in human nonsmall cell lung cancer (NSCLC) cells. Zerumbone (1) has been shown to exert anticancer activities. In this study, whether and how 1 affects OPN-induced cell invasion was determined in NSCLC A549 cells. Results from Boyden chamber assays suggested that OPN induced invasion of A549 cells and that 1 strongly suppressed this activity without affecting cell viability. Compound 1 effectively inhibited OPN-induced protein expression of ROCK1, the phosphorylation of LIM kinase 1 and 2 (LIMK1/2), and cofilin. In addition, immunofluorescence staining showed that OPN caused a significant increase in lamellipodia formation at the leading edge of cells. However, 1 dramatically decreased OPN-induced lamellipodia formation. Compound 1 impaired OPN-induced phosphorylation of FAK and AKT, as determined by Western blot analysis. Taken together, these results suggest that 1 causes considerable suppression of OPN-induced cell invasion through inhibiting the FAK/AKT/ROCK pathway in NSCLC A549 cells.
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