Antitumor activity of methyl gallate by inhibition of focal adhesion formation and Akt phosphorylation in glioma cells
Antitumor activity of methyl gallate by inhibition of focal adhesion formation and Akt phosphorylation in glioma cells
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DOI：
10.1016/j.bbagen.2013.03.030
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发表时间：
2013-08-01
影响因子：
3
通讯作者：
Choi, Soo Young
中科院分区：
文献类型：
--
作者：
Lee, Sang-Hyun;Kim, Jin Kyu;Choi, Soo Young
背景资料：没食子酸甲酯（MG）具有广泛的生物学特性，包括抗氧化、抗炎和抗微生物活性。然而，其抗肿瘤活性尚未在癌细胞中进行广泛研究。因此，我们研究了MG在谷氨酸诱导的大鼠C6和人U373胶质瘤细胞增殖和migration.Methods的效果：MG是从槭barbinerve干树皮分离。分别通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四氮唑（MTT）和划痕伤口愈合试验分析细胞活力和迁移。结果：MG处理C6和U373胶质瘤细胞后，细胞活力、迁移能力和Akt磷酸化水平均显著降低。谷氨酸刺激显著增加ERK 1/2磷酸化水平。然而，用MG处理的细胞显示ERK 1/2磷酸化降低。通过MG或MEK 1/2抑制剂抑制ERK 1/2显著抑制Ser（83）处的桩蛋白磷酸化，并且粘着斑翻转产生低效的胶质瘤细胞迁移。此外，Akt和ERK 1/2的激活谷氨酸刺激后的钙离子和蛋白激酶C活性，分别通过α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酸谷氨酸受体和代谢型谷氨酸receptor.General Significance：我们的研究结果清楚地表明，MG通过下调Alct和ERK 1/2信号通路有很强的抗肿瘤作用。因此，没食子酸甲酯是一种有效的抗肿瘤和治疗胶质瘤的新药物。(c)2013爱思唯尔有限公司版权所有。
Background: Methyl gallate (MG) possesses a wide range of biological properties that include anti-oxidant, anti-inflammatory, and anti-microbial activities. However, its anti-tumor activity has not been extensively examined in cancer cells. Thus, we examined the effect of MG in both glutamate-induced rat C6 and human U373 glioma cell proliferation and migration.Methods: MG was isolated from the stem bark of Acer barbinerve. Cell viability and migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch wound-healing assay, respectively. Focal adhesion formation was detected with immunofluorescence.Results: Treatment of C6 and U373 glioma cells with MG significantly reduced cell viability, migration, and Akt phosphorylation level. Glutamate stimulation markedly increased the level of ERK1/2 phosphorylation. However, cells treated with MG displayed decreased ERK1/2 phosphorylation. Inhibition of ERK1/2 by MG or MEK1/2 inhibitor significantly inhibited paxillin phosphorylation at Ser(83) and focal adhesion turn-over produced inefficient glioma cell migration. In addition, activation of Akt and ERK1/2 upon glutamate stimulation was independently regulated by Ca2+ and protein kinase C activity, respectively, via the alpha-amino-3-hydroxy-5-methy-4-isoxazolepropionate acid glutamate receptor and metabotropic glutamate receptor.General significance: Our results clearly indicate that MG has a strong anti-tumor effect through the down-regulation of the Alct and ERK1/2 signaling pathways. Thus, methyl gallate is a potent anti-tumor and novel therapeutic agent for glioma. (c) 2013 Elsevier B.V. All rights reserved.