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植物提取物诱导三阴性乳腺癌细胞中P53及信号转导和转录激活因子3信号通路的凋亡

Plant Extract Induces Apoptosis P53 and Signal Transducer and Activator of Transcription 3 Signaling Pathways in Triple-Negative Breast Cancer Cells.

作者信息

Fouzat Arij, Hussein Ola Jihad, Gupta Ishita, Al-Farsi Halema F, Khalil Ashraf, Al Moustafa Ala-Eddin

机构信息

College of Pharmacy, QU Health, Qatar University, Doha, Qatar.

College of Medicine, QU Health, Qatar University, Doha, Qatar.

出版信息

Front Nutr. 2022 Mar 18;9:871667. doi: 10.3389/fnut.2022.871667. eCollection 2022.

Abstract

() is used as an alternative medicine in the Middle East to manage numerous human diseases. We recently reported that flower extract inhibits cell proliferation and invasion of human oral and HER2-positive breast cancer cells. Nevertheless, the outcome of extract on triple-negative breast cancer (TNBC) cells has not been explored yet. We herein investigate the effect of the aqueous extract (100 and 200 μl/ml) on two TNBC cell lines (MDA-MB-231 and MDA-MB-436) for 48 h and explore its underlying molecular pathways. Our data revealed that extract suppresses cell proliferation by approximately 50% and alters cell-cycle progression of these two cancer cell lines. Additionally, extract induces cell apoptosis by 40-50%, accompanied by the upregulation of pro-apoptotic markers (Bax and cleaved caspase-8) and downregulation of the anti-apoptotic marker, Bcl-2. Moreover, extract inhibits colony formation compared to their matched control. More significantly, the molecular pathway analysis of -treated cells revealed that extract enhances p53 expression, while inhibiting the expression of total and phosphorylated Signal Transducer and Activator Of Transcription 3 (STAT3) in both cell lines, suggesting p53 and STAT3 are the main key players behind the biological events provoked by the extract in TNBC cells. Our findings implicate that flower extract may possess an important potential as an anticancer drug against TNBC.

摘要

()在中东地区被用作替代药物来治疗多种人类疾病。我们最近报道,[花名]提取物可抑制人口腔癌细胞和HER2阳性乳腺癌细胞的增殖和侵袭。然而,[花名]提取物对三阴性乳腺癌(TNBC)细胞的作用尚未得到研究。我们在此研究了[花名]水提取物(100和200μl/ml)对两种TNBC细胞系(MDA-MB-231和MDA-MB-436)作用48小时后的效果,并探索其潜在的分子途径。我们的数据显示,[花名]提取物可使细胞增殖抑制约50%,并改变这两种癌细胞系的细胞周期进程。此外,[花名]提取物可诱导40 - 50%的细胞凋亡,同时促凋亡标志物(Bax和裂解的caspase-8)上调,抗凋亡标志物Bcl-2下调。而且,与匹配的对照相比,[花名]提取物抑制集落形成。更显著的是,对经[花名]处理的细胞进行分子途径分析发现,[花名]提取物增强p53表达,同时抑制两种细胞系中总信号转导和转录激活因子3(STAT3)及磷酸化STAT3的表达,这表明p53和STAT3是[花名]提取物在TNBC细胞中引发生物学事件的主要关键因素。我们的研究结果表明,[花名]提取物作为一种抗TNBC的抗癌药物可能具有重要潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50b3/8971957/87db49b63be3/fnut-09-871667-g001.jpg

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