Beta-arrestin 2 modulates resveratrol-induced apoptosis and regulation of Akt/GSK3ß pathways

Biochim Biophys Acta. 2010 Sep;1800(9):912-8. doi: 10.1016/j.bbagen.2010.04.015. Epub 2010 May 7.

Abstract

Background: Resveratrol is emerging as a novel anticancer agent. However, the mechanism(s) by which resveratrol exerts its effects on endometrial cancer (EC) are unknown. We previously reported that beta-arrestin 2 plays a critical role in cell apoptosis. The role of ß-arrestin 2 in resveratrol modulation of endometrial cancer cell apoptosis remains to be established.

Scope of review: EC cells HEC1B and Ishikawa were transfected with either ß-arrestin 2 RNA interfering (RNAi) plasmid or beta-arrestin 2 full-length plasmid and control vector. The cells were then exposed to differing concentrations of resveratrol. Apoptotic cells were detected by TUNEL assay. Expression of total and phosphorylated Akt (p-Akt), total and phosphorylated glycogen synthase kinase 3 beta (p-GSK3ß), and caspase-3 were determined by Western blot analysis. Our data demonstrate that inhibition of ß-arrestin 2 increases the number of apoptotic cells and caspase-3 activation. Additionally ß-arrestin 2 exerted an additive effect on resveratrol-reduced levels of p-Akt and p-GSK3ß. Overexpression of ß-arrestin 2 decreased the percentage of apoptosis and caspase-3 activation and attenuated resveratrol-reduced levels of p-Akt and p-GSK3ß. Taken together, our studies demonstrate for the first time that ß-arrestin 2 mediated signaling plays a critical role in resveratrol-induced apoptosis in EC cells.

Major conclusions: Resveratrol primes EC cells to undergo apoptosis by modulating beta-arrestin 2 mediated Akt/GSK3ß signaling pathways.

General significance: These inspiring findings would provide a new molecular basis for further understanding of cell apoptotic mechanisms mediated by ß-arrestin 2 and may provide insights into a potential clinical relevance in EC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Arrestins / genetics
  • Arrestins / metabolism*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Activation / genetics
  • Female
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • Resveratrol
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use
  • beta-Arrestin 2
  • beta-Arrestins

Substances

  • ARRB2 protein, human
  • Antineoplastic Agents, Phytogenic
  • Arrestins
  • Stilbenes
  • beta-Arrestin 2
  • beta-Arrestins
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
  • CASP3 protein, human
  • Caspase 3
  • Resveratrol