title: Antitumor activity of methyl gallate by inhibition of focal adhesion formation and Akt phosphorylation in glioma cells.
abstract: 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin Kyu
authors.initials: JK
authors.lastname: Kim
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Hwang
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Han
authors.forename: Joa Sub
authors.initials: JS
authors.lastname: Oh
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; C052082:methyl gallate; D005707:Gallic Acid; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium