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
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
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DOI：
10.1002/mnfr.201300307
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发表时间：
2013-12-01
影响因子：
5.2
通讯作者：
de Mejia, Elvira Gonzalez
中科院分区：
文献类型：
--
作者：
Johnson, Jodee L.;de Mejia, Elvira Gonzalez
目的是检测柑橘类水果生物活性化合物对BxPC-3和PANC-1人胰腺癌细胞的抑制作用，重点是与糖原合成酶激酶-3/核因子κ B信号通路相关的黄酮类芹菜素的抗增殖作用机制。芹菜素是最有效的（对于BxPC-3，24和48小时的IC 50 = 23和12 M，对于PANC-1，24和48小时的IC 50 = 71和41 M）。芹菜素通过抑制糖原合成酶激酶-3/核因子κ B信号通路诱导胰腺细胞死亡。芹菜素将细胞周期阻滞在G（2）/M期（BxPC-3和PANC-1在50 M时分别为36%和32%），同时降低细胞周期蛋白B1的表达。芹菜素激活线粒体途径的细胞凋亡（44和14%，在50 M的BxPC-3和PANC-1，分别）和修改的凋亡蛋白的表达。芹菜素可显著上调BxPC-3细胞中IL 17 F、LTA、IL 17 C、IL 17 A和IFN-1基因的表达，上调倍数分别为114.2倍、33.1倍、23.2倍、11.3倍和8.9倍，这可能与芹菜素的抗肿瘤作用有关。
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.