Ajwa Date (Phoenix dactylifera L.) extract inhibits human breast adenocarcinoma (MCF7) cells in vitro by inducing apoptosis and cell cycle arrest
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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 downregulation 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. © 2016 Khan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Adenocarcinoma, Apoptosis, Breast neoplasms, Caspase 3, Cell cycle checkpoints, Cell proliferation, Cell shape, Dna fragmentation, Female, Gene expression regulation, neoplastic, Humans, In situ nick-end labeling, Mcf-7 cells, Membrane potential, mitochondrial, Methanol, Microscopy, phase-contrast, Neoplasm proteins, Phoeniceae, Plant extracts, Real-time polymerase chain reaction, S phase, Up-regulation, Antineoplastic agent, Date (fruit) extract, Fas antigen, Fas ligand, Plant extract, Protein bax, Protein bcl 2, Protein p53, Unclassified drug, Tumor protein, Antineoplastic activity, Antiproliferative activity, Article, Bax gene, Bcl 2 gene, Breast adenocarcinoma, Breast cancer cell line, Cancer inhibition, Cell cycle arrest, Cell structure, Cell vacuole, Concentration response, Controlled study, Date (fruit), Down regulation, Enzyme activation, Enzyme activity, Fas gene, Fasl gene, Gene expression, Human, Human cell, In vitro study, Mitochondrial membrane potential, Protein expression, S phase cell cycle checkpoint, Tumor suppressor gene, Upregulation, Breast tumor, Cell cycle checkpoint, Cell cycle s phase, Chemistry, Drug effects, Gene expression regulation, Genetics, Mcf-7 cell line, Metabolism, Pathology, Phase contrast microscopy, Phoenix (plant), Real time polymerase chain reaction, Tunel assay