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Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells

查看全文 作　　者：Mouad [1]Edderkaoui;Irina [1,2]Odinokova;Izumi [1]Ohno;Ilya [1]Gukovsky;Vay Liang W [1]Go;Stephen J [1]Pandol;Anna S [1]Gukovskaya 高影响力作者 机构地区：[1]Department of Medicine,Veterans Affairs Greater Los Angeles Healthcare System and University of California,Los Angeles CA 90073,California,United States;[2]Institute of Theoretical and Experimental Biophysics,Russian Academy of Sciences,Pushchino,Moscow Region 142290,Russia高影响力机构 出　　处：《World Journal of Gastroenterology》索引2008年第14卷第23期,共9页高影响力期刊 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. 关 键 词：胰腺癌 鞣花酸 核因子 细胞凋亡
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