Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells

J Exp Ther Oncol. 2009;8(1):25-33.

Abstract

Resveratrol (trans-3,4', 5-trihydroxystilbene) is a naturally occurring polyphenolic compound that has antiinflammatory, antioxidant, neuroprotective properties and acts as a chemopreventive agent. Resveratrol causes cell cycle arrest and induces apoptotic cell death in various types of cancer cells. In the current studies, the effect of resveratrol on phosphoinositide kinase-3 (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway was examined in human U251 glioma cells. Resveratrol decreased both the expression and phosphorylation of Akt. Inhibitors of PI3K (LY294002) and Akt (SH-6) enhanced resveratrol-induced LDH release and caspase-3 activation. Resveratrol reduced phosphorylation of ribosomal protein S6 and the mTOR inhibitor rapamycin further enhanced resveratrol-induced cell death. These results suggest that the downregulation of PI3K/Akt/mTOR signaling pathways may be an important mediator in resveratrol-induced apoptosis in glioma cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cyclin D1 / antagonists & inhibitors
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinases / drug effects*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Resveratrol
  • Signal Transduction / drug effects*
  • Stilbenes / pharmacology*
  • TOR Serine-Threonine Kinases

Substances

  • Antineoplastic Agents, Phytogenic
  • CCND1 protein, human
  • Phosphoinositide-3 Kinase Inhibitors
  • Stilbenes
  • Cyclin D1
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Caspase 3
  • Resveratrol