Flavonoid apigenin modified gene expression associated with inflammation and cancer and induced apoptosis in human pancreatic cancer cells through inhibition of GSK-3β/NF-κB signaling cascade

被引：65
作者：
Johnson, Jodee L. [1 ]
de Mejia, Elvira Gonzalez [1 ,2 ]
机构：
[1] Univ Illinois, Div Nutr Sci, Urbana, IL 61801 USA
[2] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA
来源：
MOLECULAR NUTRITION & FOOD RESEARCH | 2013年 / 57卷 / 12期
基金：
美国食品与农业研究所;
关键词：
Apigenin; Flavonoids; GSK-3; NF-B; Pancreatic cancer; FACTOR-KAPPA-B; K-RAS; EPITHELIAL-CELLS; KINASE-ACTIVITY; THERAPY; P53; TUMORIGENESIS; CHEMOTHERAPY; ACTIVATION; MECHANISMS;
D O I：
10.1002/mnfr.201300307
中图分类号：
TS2 [食品工业];
学科分类号：
0832 ;
摘要：
ScopeThe objective was to examine the inhibitory effects of citrus fruit bioactive compounds on BxPC-3 and PANC-1 human pancreatic cancer cells, focusing on the antiproliferative mechanism of action of the flavonoid apigenin related to the glycogen synthase kinase-3/nuclear factor kappa B signaling pathway. Methods and resultsFlavonoids, limonoids, phenolic acids, and ascorbic acid were tested for cytotoxic effects on BxPC-3 and PANC-1 cells; apigenin was the most potent (IC50 = 23 and 12 M for 24 and 48 h for BxPC-3 and IC50 = 71 and 41 M for 24 and 48 h for PANC-1). Apigenin induced pancreatic cell death through inhibition of the glycogen synthase kinase-3/nuclear factor kappa B signaling pathway. Apigenin arrested cell cycle at G(2)/M phase (36 and 32% at 50 M for BxPC-3 and PANC-1, respectively) with concomitant decrease in the expression of cyclin B1. Apigenin activated the mitochondrial pathway of apoptosis (44 and 14% at 50 M for BxPC-3 and PANC-1, respectively) and modified the expression of apoptotic proteins. Apigenin highly upregulated the expression of cytokine genes IL17F (114.2-fold), LTA (33.1-fold), IL17C (23.2-fold), IL17A (11.3-fold), and IFNB1 (8.9-fold) in BxPC-3 cells, which potentially contributed to the anticancer properties. ConclusionFlavonoids have a protective role in pancreatic cancer tumorigenesis.
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收藏
页码：2112 / 2127
页数：16
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