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

Biochim Biophys Acta. 2013 Aug;1830(8):4017-29. doi: 10.1016/j.bbagen.2013.03.030. Epub 2013 Apr 3.


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.

General significance: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Calcium / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Focal Adhesions / drug effects*
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology
  • Gallic Acid / therapeutic use
  • Glioma / drug therapy*
  • Glioma / pathology
  • Phosphorylation
  • Protein Kinase C / physiology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats


  • Antineoplastic Agents
  • methyl gallate
  • Gallic Acid
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • Extracellular Signal-Regulated MAP Kinases
  • Calcium