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阿朱瓦枣(Phoenix dactylifera L.)提取物通过诱导细胞凋亡和细胞周期阻滞在体外抑制人乳腺腺癌(MCF7)细胞。

Ajwa Date (Phoenix dactylifera L.) Extract Inhibits Human Breast Adenocarcinoma (MCF7) Cells In Vitro by Inducing Apoptosis and Cell Cycle Arrest.

作者信息

Khan Fazal, Ahmed Farid, Pushparaj Peter Natesan, Abuzenadah Adel, Kumosani Taha, Barbour Elie, AlQahtani Mohammed, Gauthaman Kalamegam

机构信息

Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

PLoS One. 2016 Jul 21;11(7):e0158963. doi: 10.1371/journal.pone.0158963. eCollection 2016.

Abstract

INTRODUCTION

Phoenix dactylifera L (Date palm) is a native plant of the Kingdom of Saudi Arabia (KSA) and other Middle Eastern countries. Ajwa date has been described in the traditional and alternative medicine to provide several health benefits including anticholesteremic, antioxidant, hepatoprotective and anticancer effects, but most remains to be scientifically validated. Herein, we evaluated the anticancer effects of the Methanolic Extract of Ajwa Date (MEAD) on human breast adenocarcinoma (MCF7) cells in vitro.

METHODS

MCF7 cells were treated with various concentrations (5, 10, 15, 20 and 25 mg/ml) of MEAD for 24, 48 and 72 h and changes in cell morphology, cell cycle, apoptosis related protein and gene expression were studied.

RESULTS

Phase contrast microscopy showed various morphological changes such as cell shrinkage, vacuolation, blebbing and fragmentation. MTT (2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay demonstrated statistically significant dose-dependent inhibitions of MCF7 cell proliferation from 35% to 95%. Annexin V-FITC and TUNEL assays showed positive staining for apoptosis of MCF7 cells treated with MEAD (15 mg and 25 mg for 48 h). Flow cytometric analyses of MCF7 cells with MEAD (15 mg/ml and 20 mg/ml) for 24 h demonstrated cell cycle arrest at 'S' phase; increased p53, Bax protein expression; caspase 3activation and decreased the mitochondrial membrane potential (MMP). Quantitative real time PCR (qRT-PCR) analysis showed up-regulation of p53, Bax, Fas, and FasL and down-regulation of Bcl-2.

CONCLUSIONS

MEAD inhibited MCF7 cells in vitro by the inducing cell cycle arrest and apoptosis. Our results indicate the anticancer effects of Ajwa dates, which therefore may be used as an adjunct therapy with conventional chemotherapeutics to achieve a synergistic effect against breast cancer.

摘要

引言

海枣(Phoenix dactylifera L)是沙特阿拉伯王国及其他中东国家的本土植物。传统医学和替代医学中已描述了阿久哇枣具有多种健康益处,包括抗胆固醇、抗氧化、保肝和抗癌作用,但大多数仍有待科学验证。在此,我们评估了阿久哇枣甲醇提取物(MEAD)对人乳腺腺癌(MCF7)细胞的体外抗癌作用。

方法

用不同浓度(5、10、15、20和25mg/ml)的MEAD处理MCF7细胞24、48和72小时,并研究细胞形态、细胞周期、凋亡相关蛋白和基因表达的变化。

结果

相差显微镜显示出各种形态变化,如细胞收缩、空泡化、起泡和碎片化。MTT(2-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐)试验表明,MCF7细胞增殖受到统计学上显著的剂量依赖性抑制,抑制率从35%到95%。膜联蛋白V-FITC和TUNEL试验显示,用MEAD(15mg和25mg,处理48小时)处理的MCF7细胞凋亡呈阳性染色。用MEAD(15mg/ml和20mg/ml)处理MCF7细胞24小时的流式细胞术分析表明,细胞周期停滞在“S”期;p53、Bax蛋白表达增加;半胱天冬酶3激活,线粒体膜电位(MMP)降低。定量实时PCR(qRT-PCR)分析显示p53、Bax、Fas和FasL上调,Bcl-2下调。

结论

MEAD通过诱导细胞周期停滞和凋亡在体外抑制MCF7细胞。我们的结果表明阿久哇枣具有抗癌作用,因此可作为传统化疗的辅助治疗,以实现对乳腺癌的协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e07/4956039/80aee259eebc/pone.0158963.g001.jpg

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