Epigalocatechin-3-gallate (EGCG) downregulates PEA15 and thereby augments TRAIL-mediated apoptosis in malignant glioma

Neurosci Lett. 2008 Dec 19;448(1):161-5. doi: 10.1016/j.neulet.2008.10.036. Epub 2008 Oct 17.

Abstract

EGCG is a flavonoid that exhibited therapeutic activity in cancer. In this study three glioblastoma cell lines (U87, A172 and U251) were treated with EGCG, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of both. Treatment with subtoxic doses of EGCG in combination with TRAIL induces rapid apoptosis in TRAIL-resistant glioma cells, suggesting that this combined treatment may offer an attractive strategy for treating gliomas. EGCG treatment down-regulated phosphoprotein-enriched in astrocytes (PEA15) through an Akt (PKB)-dependent mechanism. In addition, over-expression of PEA15 attenuated cytotoxicity induced by the combination of EGCG and TRAIL. In summary, PEA15 is a key regulator in TRAIL-EGCG-mediated cell death in malignant glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins
  • Caspase 7 / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glioma / pathology
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Phosphoproteins / metabolism
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*

Substances

  • Antioxidants
  • Apoptosis Regulatory Proteins
  • BIRC5 protein, human
  • Enzyme Inhibitors
  • Inhibitor of Apoptosis Proteins
  • Intracellular Signaling Peptides and Proteins
  • Microtubule-Associated Proteins
  • PEA15 protein, human
  • Phosphoproteins
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand
  • Catechin
  • epigallocatechin gallate
  • Caspase 7