Antitumor activity of methyl gallate by inhibition of focal adhesion formation and Akt phosphorylation in glioma cells |
| |
Authors: | 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 |
| |
Institution: | 1. Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Republic of Korea;2. Natural Products Research Institute, Gyeonggi Institute of Science & Technology Promotion, Suwon 443-270, Republic of Korea;3. College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea |
| |
Abstract: | BackgroundMethyl 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.MethodsMG 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.ResultsTreatment 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 Ser83 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 α-amino-3-hydroxy-5-methy-4-isoxazolepropionate acid glutamate receptor and metabotropic glutamate receptor.General significanceOur 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. |
| |
Keywords: | Methyl gallate Glioma Cell migration Glutamate Focal adhesion |
本文献已被 ScienceDirect 等数据库收录! |
|