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杨梅素通过激活 BRCA1-GADD45 通路对 MCF-7 乳腺癌细胞发挥凋亡作用。

Myricetin Exerts its Apoptotic Effects on MCF-7 Breast Cancer Cells through Evoking the BRCA1-GADD45 Pathway.

机构信息

Department of Anatomical Sciences, Isfahan University of Medical Sciences, Iran.

Institute for Advanced Studies in Basic Sciences, Zanjan, Iran.

出版信息

Asian Pac J Cancer Prev. 2020 Dec 1;21(12):3461-3468. doi: 10.31557/APJCP.2020.21.12.3461.

Abstract

OBJECTIVE

Myricetin is a polyphenol flavonoid with nutraceutical values which is abundantly found as the main ingredient of various foods and beverages. It has been reported that the function of myricetin is to trigger apoptosis in several types of cancers. The present study intended to investigate the apoptotic effects of myricetin on MCF-7 breast cancer cells and to assess its possible mechanisms of action.

MATERIALS AND METHODS

MCF-7 breast cancer cells were assigned to four groups: Control (cells in normal condition); myricetin (cells treated with the IC50 dosage of myricetin) in three different incubation times (24, 48, and 72 h). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V assay, flow cytometry, real-time polymerase chain reaction (PCR), and caspase-3 assay were used to estimate the apoptosis function of myricetin in breast cancer.

RESULTS

The expression levels of apoptosis-related genes caspase-3, caspase-8, caspase-9, and the BAX /Bcl-2 ratio as well as the expression of p53, BRCA1, GADD45 genes were significantly increased following the treatment of MCF-7 breast cancer cells with myricetin. The annexin V assay demonstrated the significant expression of annexin which was also detected by flow cytometry.

CONCLUSION

Myricetin efficiently induces apoptosis in MCF-7 breast cancer cells by evoking both extrinsic and intrinsic apoptotic pathways. Myricetin may exert its apoptotic effects on MCF-7 cells by inducing the BRCA1- GADD45 pathway.
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摘要

目的

杨梅素是一种具有营养保健品价值的多酚类黄酮,大量存在于各种食品和饮料中,是其主要成分。据报道,杨梅素的功能是触发几种类型癌症的细胞凋亡。本研究旨在探讨杨梅素对 MCF-7 乳腺癌细胞的凋亡作用,并评估其可能的作用机制。
材料与方法:将 MCF-7 乳腺癌细胞分为四组:对照组(细胞处于正常状态);杨梅素组(用杨梅素的 IC50 剂量处理的细胞),在三个不同的孵育时间(24、48 和 72 h)。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)测定法、膜联蛋白 V 测定法、流式细胞术、实时聚合酶链反应(PCR)和 caspase-3 测定法来评估杨梅素对乳腺癌的凋亡作用。
结果:杨梅素处理 MCF-7 乳腺癌细胞后,细胞中与细胞凋亡相关的基因 caspase-3、caspase-8、caspase-9 的表达水平以及 BAX/Bcl-2 比值和 p53、BRCA1、GADD45 基因的表达均显著增加。膜联蛋白 V 测定法显示膜联蛋白的表达显著增加,流式细胞术也检测到了这一点。
结论:杨梅素通过诱导外源性和内源性凋亡途径,有效地诱导 MCF-7 乳腺癌细胞凋亡。杨梅素可能通过诱导 BRCA1-GADD45 途径对 MCF-7 细胞发挥其凋亡作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f851/8046300/96db23bc081a/APJCP-21-3461-g001.jpg

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