Antitumor activity of methyl gallate by inhibition of focal adhesion formation and Akt phosphorylation in glioma cells.

Sang-Hyun Lee, Jin Kyu Kim, Dae Won Kim, Hyun Sook Hwang, Won Sik Eum, Jinseu Park, Kyu Hyung Han, Joa Sub Oh, Soo Young Choi

Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Republic of Korea.

Biochimica et biophysica acta 2013 Aug

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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. 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. 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 Ca(2+) and protein kinase C activity, respectively, via the α-amino-3-hydroxy-5-methy-4-isoxazolepropionate acid glutamate receptor and metabotropic glutamate receptor. Our results clearly indicate that MG has a strong anti-tumor effect through the down-regulation of the Akt and ERK1/2 signaling pathways. Thus, methyl gallate is a potent anti-tumor and novel therapeutic agent for glioma. Copyright © 2013 Elsevier B.V. All rights reserved.

Citation

Sang-Hyun Lee, Jin Kyu Kim, Dae Won Kim, Hyun Sook Hwang, Won Sik Eum, Jinseu Park, Kyu Hyung Han, Joa Sub Oh, Soo Young Choi. Antitumor activity of methyl gallate by inhibition of focal adhesion formation and Akt phosphorylation in glioma cells. Biochimica et biophysica acta. 2013 Aug;1830(8):4017-29