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山金车二醇水提物诱导 MDA-MB-231 乳腺癌细胞凋亡和 G2/M 细胞周期阻滞。

Bryonia dioica aqueous extract induces apoptosis and G2/M cell cycle arrest in MDA‑MB 231 breast cancer cells.

机构信息

Laboratory Research on Biological Systems and Geomatics, Faculty of Nature and Life, University of Mascara, Mascara 29000, Algeria.

Zoology Department, Faculty of Science Beni‑Suef University, Beni‑Suef 62511, Egypt.

出版信息

Mol Med Rep. 2019 Jul;20(1):73-80. doi: 10.3892/mmr.2019.10220. Epub 2019 May 9.

Abstract

Bryonia dioica Jacq. is a climbing perennial herb with tuberous roots which is widely used in traditional medicine in Algeria for the treatment of cancer. The present study aimed to evaluate the apoptogenic activity and phytochemical composition of the aqueous extract of B. dioica roots growing in Algeria. The cytotoxic effect of B. dioica aqueous decoction against breast cancer MDA‑MB‑231 cells was evaluated by an MTT assay. Apoptosis induction was assessed by an Annexin V‑fluorescien iosthiocyanate assay. Propidium iodide staining of cell DNA was used to assess the effects on the cell cycle. In addition to UV‑Visible (UV‑vis) analysis, the major compounds of the extracts were determined using liquid chromatography‑mass spectrometric analyses. Our results showed that the B. dioica aqueous extract induced cell death in a time‑dependent manner. The highest inhibitory effect was produced at concentrations of 50 µg/ml or higher after 72 h of treatment (91.15±0.71%). Furthermore, the extract induced apoptosis of MDA‑MB‑231 cells. At 250 µg/ml, 64.61% of the treated MDA‑MB‑231 cells were apoptotic. This was accompanied by cell cycle arrest at G2/M phase. The percentage of cells in G2/M increased from 15.7% (untreated cells) to 59.13% (50 µg/ml) and 58.51% (250 µg/ml). The UV‑vis absorption spectra of B. dioica aqueous extract showed two absorption bands characteristic of the flavonol skeleton; 350‑385 nm (Band I) and 250‑280 nm (Band II). Myricetin (2,5,7,3,4,5‑pentahydroxylflavonol) was found to be the major compound in the B. dioica aqueous extract. These findings suggest that B. dioica could be considered a promising source for developing novel therapeutics against breast cancer.

摘要

欧洲防己苦素(Bryonia dioica Jacq.)是一种攀援多年生草本植物,具有块根,在阿尔及利亚的传统医学中被广泛用于治疗癌症。本研究旨在评估生长在阿尔及利亚的欧洲防己苦素根的促凋亡活性和植物化学成分。通过 MTT 测定评估欧洲防己苦素水提物对乳腺癌 MDA-MB-231 细胞的细胞毒性作用。通过 Annexin V-荧光素碘化丙啶(PI)染色法评估细胞凋亡诱导。细胞 DNA 的碘化丙啶(PI)染色用于评估对细胞周期的影响。除了紫外可见(UV-vis)分析外,还使用液相色谱-质谱联用分析确定提取物中的主要化合物。我们的结果表明,欧洲防己苦素水提物呈时间依赖性诱导细胞死亡。在 72 小时的处理后,浓度为 50 µg/ml 或更高时产生最高的抑制作用(91.15±0.71%)。此外,该提取物诱导 MDA-MB-231 细胞凋亡。在 250 µg/ml 时,处理的 MDA-MB-231 细胞中有 64.61%为凋亡细胞。这伴随着细胞周期停滞在 G2/M 期。G2/M 期的细胞百分比从 15.7%(未处理细胞)增加到 59.13%(50 µg/ml)和 58.51%(250 µg/ml)。欧洲防己苦素水提物的紫外可见吸收光谱显示两个特征黄酮醇骨架的吸收带;350-385nm(带 I)和 250-280nm(带 II)。在欧洲防己苦素水提物中发现的主要化合物是杨梅素(2,5,7,3,4,5-六羟基黄酮醇)。这些发现表明,欧洲防己苦素可被视为开发针对乳腺癌的新型治疗方法的有前途的来源。

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