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通过抑制NF-κB信号通路抑制MDA-MB-231细胞的增殖、阻滞细胞周期并诱导其凋亡。

Inhibits Cell Proliferation, Arrests Cell Cycle, and Induces Apoptosis in MDA-MB-231 Cells through Suppression of the NF-κB Pathway.

作者信息

Batool Riffat, Aziz Ejaz, Tan Benny K-H, Mahmood Tariq

机构信息

Department of Plant Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

出版信息

Front Pharmacol. 2017 Oct 12;8:731. doi: 10.3389/fphar.2017.00731. eCollection 2017.

DOI:10.3389/fphar.2017.00731
PMID:29075192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5643984/
Abstract

, commonly known as tooth docked, is widely used in traditional system of medicines. Although it is well reported for its biological activities and medicinal value, only few studies have been carried out to assess its anticancer potential. This study seeks to evaluate the anticancer activity of leaf extracts of against breast cancer MDA-MB-231 cell line, a triple negative human breast cancer cell line with invasive properties and to identify the molecular targets underlying its mechanism of action. Cytotoxicity of plant extracts was determined against breast cancer cells, using the MTT assay. Flow cytometry was performed to analyze the changes in cell cycle and apoptotic effect, if any. Cells were also studied for their wound healing and invasive potential as well as for Western blotting of apoptotic genes and nuclear factor-kappaB (NF-κB) pathway. The results revealed that methanol (RM) and chloroform (RC) extracts of had the highest inhibition of cell proliferation in a concentration- and time-dependent manner. This inhibitory effect was found to be linked to arrest of cell cycle at the G0/G1 phase, along with induction of apoptosis and accumulation in the sub-G1 phase. Moreover, it was shown that both RM and RC inhibited the proliferation of the malignant cells and induced apoptosis by repressing the activation of NF-κB and its subsequent transcripts, Bcl-xl, Bcl-2, Cyclin D1, survivin, and XIAP. Apoptosis was also confirmed in the cells as suggested by caspase-3 detection. RM and RC also abrogated IκBa phosphorylation in the malignant cells as well as reduced the invasive and migratory capabilities of these cells. Our findings suggest that the methanol and chloroform extracts of may have anti-cancer compounds that are potentially useful in the treatment of human breast cancer.

摘要

(此处原文缺失植物名称),通常被称为牙对接,在传统医学体系中广泛使用。尽管其生物活性和药用价值已有大量报道,但评估其抗癌潜力的研究却很少。本研究旨在评估(此处原文缺失植物名称)叶提取物对乳腺癌MDA - MB - 231细胞系(一种具有侵袭特性的三阴性人乳腺癌细胞系)的抗癌活性,并确定其作用机制的分子靶点。使用MTT法测定植物提取物对乳腺癌细胞的细胞毒性。进行流式细胞术分析细胞周期变化和凋亡效应(如有)。还研究了细胞的伤口愈合和侵袭潜力,以及凋亡基因和核因子 - κB(NF - κB)途径的蛋白质印迹分析。结果显示,(此处原文缺失植物名称)的甲醇(RM)和氯仿(RC)提取物以浓度和时间依赖性方式对细胞增殖具有最高抑制作用。发现这种抑制作用与细胞周期在G0/G1期停滞有关,同时诱导凋亡并在亚G1期积累。此外,结果表明RM和RC均通过抑制NF - κB及其后续转录本Bcl - xl、Bcl - 2、细胞周期蛋白D1、生存素和XIAP的激活来抑制恶性细胞的增殖并诱导凋亡。如通过caspase - 3检测所表明的,细胞凋亡也得到证实。RM和RC还消除了恶性细胞中IκBa的磷酸化,并降低了这些细胞的侵袭和迁移能力。我们的研究结果表明,(此处原文缺失植物名称)的甲醇和氯仿提取物可能含有抗癌化合物,对治疗人类乳腺癌具有潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cd/5643984/a4e9f9cbd889/fphar-08-00731-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cd/5643984/2af2109852c9/fphar-08-00731-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cd/5643984/2e8b19bc1b23/fphar-08-00731-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cd/5643984/3c791f9da37b/fphar-08-00731-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cd/5643984/f2b55fcc7075/fphar-08-00731-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cd/5643984/484aafdffd02/fphar-08-00731-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cd/5643984/a4e9f9cbd889/fphar-08-00731-g010.jpg

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