Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell line

Cancer Lett. 2007 Dec 8;258(1):144-53. doi: 10.1016/j.canlet.2007.08.020. Epub 2007 Oct 17.

Abstract

The aim of this investigation was to evaluate the chemopreventative/antiproliferative potential of a grape seed proanthocyanidin extract (GSPE) against colon cancer cells (CaCo2 cells) and to investigate its mechanism of action. GSPE (10-100 microg/ml) significantly inhibited cell viability and increased apoptosis in CaCo2 cells, but did not alter viability in the normal colon cell line (NCM460). The increased apoptosis observed in GSPE-treated CaCo2 cells correlated with an attenuation of PI3-kinase (p110 and p85 subunits) and decreased PKB Ser(473) phosphorylation. GSPE might thus exert its beneficial effects by means of increased apoptosis and suppression of the important PI3-kinase survival-related pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Caco-2 Cells / drug effects
  • Caco-2 Cells / enzymology
  • Caco-2 Cells / pathology
  • Cell Survival / drug effects
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Proanthocyanidins / pharmacology*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • Seeds / chemistry*
  • Vitis / chemistry*

Substances

  • Antioxidants
  • Phosphoinositide-3 Kinase Inhibitors
  • Proanthocyanidins
  • proanthocyanidin
  • 3-Phosphoinositide-Dependent Protein Kinases
  • Protein-Serine-Threonine Kinases