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橄榄苦苷通过阻断 NF-κB 激活级联反应诱导雌激素受体阴性乳腺癌细胞凋亡。

Oleuropein induces apoptosis via abrogating NF-κB activation cascade in estrogen receptor-negative breast cancer cells.

机构信息

Department of Pharmacology, Medical School of Yangtze University, Jingzhou, China.

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

出版信息

J Cell Biochem. 2019 Mar;120(3):4504-4513. doi: 10.1002/jcb.27738. Epub 2018 Sep 27.

Abstract

Oleuropein is one of the most abundant phenolic compounds found in olives. Epidemiological studies have indicated that an increasing intake of olive oil can significantly reduce the risk of breast cancer. However, the potential effect(s) of oleuropein on estrogen receptor (ER)-negative breast cancer is not fully understood. This study aims to understand the anticancer effects and underlying mechanism(s) of oleuropein on ER-negative breast cancer cells in vitro. The effect of oleuropein on the viability of breast cancer cell lines was examined by mitochondrial dye-uptake assay, apoptosis by flow cytometric analysis, nuclear factor-κB (NF-κB) activation by DNA binding/reporter assays and protein expression by Western blot analysis. In the present report, thiazolyl blue tetrazolium bromide assay results indicated that oleuropein inhibited the viability of breast cancer cells, and its effects were more pronounced on MDA-MB-231 as compared with MCF-7 cells. It was further found that oleuropein increased the level of reactive oxygen species and also significantly inhibited cellular migration and invasion. In addition, the activation of NF-κB was abrogated as demonstrated by Western blot analysis, NF-κB-DNA binding, and luciferase assays. Overall, the data indicates that oleuropein can induce substantial apoptosis via modulating NF-κB activation cascade in breast cancer cells.

摘要

橄榄苦苷是橄榄中含量最丰富的酚类化合物之一。流行病学研究表明,增加橄榄油的摄入量可以显著降低乳腺癌的风险。然而,橄榄苦苷对雌激素受体(ER)阴性乳腺癌的潜在作用尚不完全清楚。本研究旨在体外研究橄榄苦苷对 ER 阴性乳腺癌细胞的抗癌作用及其潜在机制。通过线粒体染料摄取试验、流式细胞术分析细胞凋亡、DNA 结合/报告试验检测核因子-κB(NF-κB)的激活以及 Western blot 分析检测蛋白表达来检测橄榄苦苷对乳腺癌细胞系活力的影响。在本报告中,噻唑蓝溴化四氮唑(MTT)比色法结果表明,橄榄苦苷抑制了乳腺癌细胞的活力,并且其对 MDA-MB-231 细胞的作用比 MCF-7 细胞更为明显。进一步研究发现,橄榄苦苷增加了活性氧的水平,并且还显著抑制了细胞迁移和侵袭。此外,Western blot 分析、NF-κB-DNA 结合和荧光素酶试验表明,NF-κB 的激活被阻断。综上所述,数据表明橄榄苦苷可以通过调节 NF-κB 激活级联反应诱导乳腺癌细胞发生实质性凋亡。

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