Korean Scutellaria baicalensis water extract inhibits cell cycle G1/S transition by suppressing cyclin D1 expression and matrix-metalloproteinase-2 activity in human lung cancer cells
Korean Scutellaria baicalensis water extract inhibits cell cycle G1/S transition by suppressing cyclin D1 expression and matrix-metalloproteinase-2 activity in human lung cancer cells
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DOI：
10.1016/j.jep.2010.10.057
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发表时间：
2011-01-27
影响因子：
5.4
通讯作者：
Kim, Gon-Sup
中科院分区：
文献类型：
--
作者：
Park, Kwang-Il;Park, Hyeon-Soo;Kim, Gon-Sup
研究目的：黄芩是一种在包括韩国在内的几个亚洲国家广泛使用的草药。黄芩的各种药用特性包括抗菌，抗病毒，抗炎和抗癌作用。本研究探讨了黄芩水提取物（SBWE）对A549非小细胞肺癌细胞的细胞毒作用、细胞周期蛋白D1（cyclin D1）、细胞周期蛋白依赖性激酶4（cyclin dependent kinase 4，CDK 4）和基质金属蛋白酶2（matrix metalloproteinase-2，MMP-2）的表达、对细胞周期进程（尤其是G1/S期）和细胞运动的影响。SBWE细胞毒性通过标准比色测定法利用3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物（MTT）进行评估，并通过Western印迹分析评估SBWE处理的A549细胞中细胞周期蛋白D1和CDK 4蛋白的表达。流式细胞术分析SBWE对A549细胞周期进程的影响。酶谱法检测A549细胞MMP-2活性;细胞运动和迁移进行了评估，通过划痕伤口愈合assay.Results：SBWE没有细胞毒性。细胞周期蛋白D1，CDK 4和MMP-2活性的产生以SBWE剂量依赖性方式显著降低，最大抑制发生在SBWE浓度为250 μ g/ml和500 μ g/ml时。结论：Cyclin D1蛋白可能与MMP-2活性和细胞运动有关。因此，SBWE通过下调细胞周期蛋白D1促进对MMP-2介导的转移和细胞增殖的强保护作用。SBWE可能是一种有效的肺癌化疗药物。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Aim of the study: Scutellaria baicalensis Georgi is a widely used medicinal herb in several Asian countries including Korea. The various medicinal properties attributed to Scutellaria baicalensis include anti-bacterial, anti-viral, anti-inflammatory and anti-cancer effects. The present study investigated the cytotoxicity of Scutellaria baicalensis water extract (SBWE) on A549 non-small-cell-lung cancer cells and the A549 expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and matrix metalloproteinase-2 (MMP-2), and the effects of SBWE on cell cycle progression, especially the G1/S phase, and on cell motility.Materials and methods: SBWE cytotoxicity was assessed by a standard colorimetric assay utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and expression of cyclin D1 and CDK4 protein in SBWE-treated A549 cells was assessed by Western blot analysis. Flow cytometry analysis was performed to determine the effect of SBWE on A549 cell cycle progression. A549 cell MMP-2 activity was examined by zymography. Cell motility and migration was assessed by a scratch wound healing assay.Results: SBWE was not cytotoxic. The production of Cyclin D1, CDK4 and MMP-2 activity were significantly decreased in a SBWE dose-dependent manner, with maximum inhibition occurring at SBWE concentrations of 250 mu g/ml and 500 mu g/ml. SBWE inhibited cell cycle progression in the G1/S phase and significantly inhibited the motility of A549 cells.Conclusions: Cyclin D1 protein may be associated with MMP-2 activity and cell motility. Thus, SBWE promotes a strong protective effect against MMP-2 mediated metastasis and cell proliferation through the down-regulation of cyclin D1. SBWE may be a useful chemotherapeutic agent for lung cancer. (C) 2010 Elsevier Ireland Ltd. All rights reserved.