Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jun 21, 2008; 14(23): 3672-3680
Published online Jun 21, 2008. doi: 10.3748/wjg.14.3672
Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells
Mouad Edderkaoui, Irina Odinokova, Izumi Ohno, Ilya Gukovsky, Vay Liang W Go, Stephen J Pandol, Anna S Gukovskaya
Mouad Edderkaoui, Irina Odinokova, Izumi Ohno, Ilya Gukovsky, Vay Liang W Go, Stephen J Pandol, Anna S Gukovskaya, Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System and University of California, Los Angeles CA 90073, California, United States
Irina Odinokova, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia
Author contributions: Edderkaoui M and Gukovskaya AS designed research; Edderkaoui M, Odinokova I, Ohno I and Gukovsky I performed research; Edderkaoui M, Go VLW, Pandol SJ and Gukovskaya AS analyzed data; Edderkaoui M and Gukovskaya AS wrote the paper.
Correspondence to: Anna S Gukovskaya, PhD, VA Greater Los Angeles Healthcare System, West Los Angeles VA Healthcare Center, 11301 Wilshire Blvd, Blg 258, Rm 340, Los Angeles CA 90073, United States.
Telephone: +1-310-4783711-41525
Fax: +1-310-2684578
Received: December 26, 2007
Revised: April 25, 2008
Accepted: May 2, 2008
Published online: June 21, 2008

AIM: To determine the effect of ellagic acid on apop-tosis 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 κB (NF-κB) 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-κB binding activity. Furthermore, inhibition of NF-κB 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 prosu-rvival transcription factor NF-κB.

Keywords: Ellagic acid, Nuclear factor-κB, Apoptosis, Pancreatic cancer