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.

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.

• 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
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1830 Issue 8 Pg. 4017-29 (Aug 2013) ISSN: 0006-3002 [Print] Netherlands
• PMID: 23562553 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Brain Neoplasms (drug therapy, 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, pharmacology, therapeutic use)
• Glioma (drug therapy, pathology)
• Phosphorylation
• Protein Kinase C (physiology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats