黄酮类芹菜素通过抑制GSK-3β/NF-κB信号级联反应来改变与炎症和癌症相关的基因表达，并诱导人胰腺癌细胞凋亡。

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.

作者信息

Johnson Jodee L, de Mejia Elvira Gonzalez

机构信息

Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, IL, USA.

出版信息

Mol Nutr Food Res. 2013 Dec;57(12):2112-27. doi: 10.1002/mnfr.201300307. Epub 2013 Aug 14.

DOI:10.1002/mnfr.201300307

PMID:23943362

Abstract

SCOPE

The 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-3β/nuclear factor kappa B signaling pathway.

METHODS AND RESULTS

Flavonoids, 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 μM for 24 and 48 h for BxPC-3 and IC50 = 71 and 41 μM for 24 and 48 h for PANC-1). Apigenin induced pancreatic cell death through inhibition of the glycogen synthase kinase-3β/nuclear factor kappa B signaling pathway. Apigenin arrested cell cycle at G2 /M phase (36 and 32% at 50 μM 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 μM 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.

CONCLUSION

Flavonoids have a protective role in pancreatic cancer tumorigenesis.

摘要

范围

目的是研究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，重点关注黄酮类芹菜素与糖原合酶激酶-3β/核因子κB信号通路相关的抗增殖作用机制。

方法和结果

测试了黄酮类化合物、柠檬苦素、酚酸和抗坏血酸对BxPC-3和PANC-1细胞的细胞毒性作用；芹菜素的作用最强（BxPC-3细胞在24小时和48小时的IC50分别为23 μM和12 μM，PANC-1细胞在24小时和48小时的IC50分别为71 μM和41 μM）。芹菜素通过抑制糖原合酶激酶-3β/核因子κB信号通路诱导胰腺细胞死亡。芹菜素使细胞周期停滞在G2/M期（50 μM时，BxPC-3和PANC-1细胞分别为36%和32%），同时细胞周期蛋白B1的表达降低。芹菜素激活凋亡的线粒体途径（50 μM时，BxPC-3和PANC-1细胞分别为44%和14%）并改变凋亡蛋白的表达。芹菜素高度上调BxPC-3细胞中细胞因子基因IL17F（114.2倍）、LTA（33.1倍）、IL17C（23.2倍）、IL17A（11.3倍）和IFNB1（8.9倍）的表达，这可能有助于其抗癌特性。