Forschungsdatenbank PMU-SQQUID

PMU-Autor/inn/en

Abstract

We investigated the effect of resveratrol on proliferation and induction of apoptosis of INS-1E rat insulinoma cells by cell counting, crystal violet staining, flow cytometry and immunoblotting. Resveratrol treatment of INS-1E cells at concentrations >= 50 mu M resulted in a dose-dependent inhibition of cell proliferation, accumulation of the cells in the S and G0/G1 phase and a significant increase of the percentage of apoptotic cells. This was paralleled by an increase of cell granularity, apoptotic volume decrease (AVD), exposure of phosphatidylserine at the outer leaflet of the plasma membrane, an increase of the 7-AAD signal and caspase activation. The AMP-kinase (AMPK) inhibitor compound C (10 mu M) significantly inhibited cell proliferation and induced caspase activation within 48 hours but this effect was not modified by resveratrol suggesting that AMPK is not a major target involved in mediating the proapoptotic effect of resveratrol in INS-1E cells. Immunoblotting revealed a significant inhibition of Akt (PKB) phosphorylation by 100 mu M resveratrol within 1 hour. Addition of insulin (10 mu M) to the culture medium strongly enhanced basal Akt phosphorylation. This enhancement was significantly attenuated by 50 and 100 mu M resveratrol. We conclude that the antiproliferative/proapoptotic effect of resveratrol on INS-1E cells is due to negative interference with Akt signaling and most likely disruption of auto/paracrine insulin signaling. Copyright (C) 2009 S. Karger AG, Basel

Useful keywords (using NLM MeSH Indexing)

Animals

Apoptosis*

Caspases/metabolism

Cell Cycle

Cell Line, Tumor

Dactinomycin/analogs*

derivatives

Dactinomycin/metabolism

Dactinomycin/pharmacology

Insulin/pharmacology

Insulin-Secreting Cells/cytology

Insulin-Secreting Cells/drug effects*

Insulin-Secreting Cells/metabolism

Insulinoma

Pancreatic Neoplasms

Phosphatidylserines/metabolism

Phosphatidylserines/pharmacology

Phosphorylation

Proto-Oncogene Proteins c-akt/metabolism

Rats

Signal Transduction

Stilbenes/pharmacology*

Time Factors

Find related publications in this database (Keywords)