Effects of green tea extract on lung cancer A549 cells: proteomic identification of proteins associated with cell migration.

Effects of green tea extract on lung cancer A549 cells: proteomic identification of proteins associated with cell migration.
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DOI:
10.1002/pmic.200800019
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发表时间:
2009-02
期刊:
影响因子:
3.4
通讯作者:
Rao, Jian Yu
Rao, Jian Yu
中科院分区:
生物学3区
文献类型:
--
作者:
Lu, Qing-Yi;Yang, Yanan;Jin, Yu Sheng;Zhang, Zuo-Feng;Heber, David;Li, Frederick P.;Dubinett, Steven M.;Sondej, Melissa A.;Loo, Joseph A.;Rao, Jian Yu

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绿茶多酚具有多种抗肿瘤活性,其作用机制尚不完全清楚。此前,我们报道了绿茶提取物(GTE)诱导的肌动蛋白重塑与A549肺癌细胞的细胞黏附增加和运动性降低有关。为了确定绿茶诱导肌动蛋白重塑的细胞靶点,我们对GTE暴露前后的A549细胞进行了双向凝胶电泳液相色谱串联质谱分析。我们已经确定了14个蛋白质点在GTE处理后表达发生变化(≥2倍)。这些蛋白质参与钙结合、细胞骨架和运动、新陈代谢、解毒或基因调控。特别是,我们发现了几个调控肌动蛋白重塑和细胞迁移的基因上调,包括层蛋白A/C。我们的数据表明,GTE诱导的层蛋白A/C上调似乎是在转录水平上,表达增加导致细胞活力下降,siRNA证实了这一点。研究结果表明,GTE改变了与A549细胞生长、运动和凋亡相关的多种蛋白质的水平,这些蛋白质的鉴定可能解释了GTE的多重抗肿瘤活性。
Green tea polyphenols exhibit multiple anti-tumor activities, and the mechanisms of action are not completely understood. Previously, we reported that green tea extract (GTE)-induced actin remolding is associated with increased cell adhesion and decreased motility in A549 lung cancer cells. To identify the cellular targets responsible for green tea-induced actin remodeling, we performed two-dimensional gel electrophoresis LC-tandem mass spectrometry of A549 cells before and after GTE exposure. We have identified 14 protein spots that changed in expression (≥2 fold) after GTE treatment. These proteins are involved in calcium-binding, cytoskeleton and motility, metabolism, detoxification or gene regulation. In particular we found up-regulation of several genes that modulate actin remodeling and cell migration, including lamin A/C. Our data indicated that GTE-induced lamin A/C up-regulation appears to be at the transcriptional level and the increased expression results in the decrease in the cell motility, as confirmed by siRNA. The result of the study demonstrates that GTE alters the levels of many proteins involved in growth, motility and apoptosis of A549 cells and their identification may explain the multiple anti-tumor activities of GTE.
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