Ellagic Acid Induces Apoptosis Through Inhibition of Nuclear Factor Kappa B in Pancreatic Cancer Cells

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2008 Jul 3

PMID 18595134

Citations 39

Authors

Mouad Edderkaoui

Irina Odinokova

Izumi Ohno

Ilya Gukovsky

Vay Liang W Go

Stephen J Pandol

Anna S Gukovskaya

Affiliations

Soon will be listed here.

Abstract

Aim: To determine the effect of ellagic acid on apoptosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid.

Methods: The effect of ellagic acid on apoptosis was assessed by measuring phosphatidylserine externalization, caspase activity, mitochondrial membrane potential and DNA fragmentation; and proliferation by measuring DNA thymidine incorporation. Mitochondrial membrane potential was measured in permeabilized cells, and in isolated mitochondria. Nuclear factor kappa B (NF-kappa B) activity was measured by electromobility shift assay (EMSA).

Results: We show that ellagic acid, a polyphenolic compound in fruits and berries, at concentrations 10 to 50 mmol/L stimulates apoptosis in human pancreatic adenocarcinoma cells. Further, ellagic acid decreases proliferation by up to 20-fold at 50 mmol/L. Ellagic acid stimulates the mitochondrial pathway of apoptosis associated with mitochondrial depolarization, cytochrome C release, and the downstream caspase activation. Ellagic acid does not directly affect mitochondria. Ellagic acid dose-dependently decreased NF-kappa B binding activity. Furthermore, inhibition of NF-kappa B activity using IkB wild type plasmid prevented the effect of ellagic acid on apoptosis.

Conclusion: Our data indicate that ellagic acid stimulates apoptosis through inhibition of the prosurvival transcription factor NF-kappa B.

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