Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells
Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells作者机构:Department of MedicineVeterans Affairs Greater Los Angeles Healthcare System and University of CaliforniaLos Angeles CA 90073CaliforniaUnited States Institute of Theoretical and Experimental BiophysicsRussian Academy of SciencesPushchinoMoscow Region 142290Russia
出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))
年 卷 期:2008年第14卷第23期
页 面:3672-3680页
核心收录:
学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金:the Department of Veterans Affairs Merit Review (to A.S.G) the Hirshberg foundation and the NIH/NCCAM (1P01AT003960-01)
摘 要: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 kB(NF-kB) 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 caspaseactivation. Ellagic acid does not directly affect mitochondria. Ellagic acid dose-dependently decreased NF-kB binding activity. Furthermore,inhibition of NF-kB 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-kB.