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芹黄素-C通过凋亡机制降低MDA-MB-231乳腺癌细胞的活力。

Avenanthramide-C reduces the viability of MDA-MB-231 breast cancer cells through an apoptotic mechanism.

作者信息

Hastings Jordan, Kenealey Jason

机构信息

Department of Nutrition, Dietetics, and Food Science, Brigham Young University, ESC S249, Provo, UT 84602 USA.

出版信息

Cancer Cell Int. 2017 Oct 18;17:93. doi: 10.1186/s12935-017-0464-0. eCollection 2017.

Abstract

BACKGROUND

Avenanthramides (AVN) are a relatively unstudied family of phytochemicals that could be novel chemotherapeutics. These compounds, found in oats, are non-toxic to healthy cells and have been shown to reduce viability of human colon and liver cancers in vitro. However, these studies do not elucidate a molecular mechanism for individual AVN. In this study we aim to see the effects of AVN on MDA-MB-231 breast cancer cells.

METHODS

An MTT assay was used to determine cell viability. Staining and analysis with a flow cytometer was used to identify cell cycle progression and apoptosis. FloJo software was used to analyze the cytometric data. In all experiments, statistical significance was determined by a two-tailed t test.

RESULTS

This study demonstrates that AVN-A, B, and C individually reduce viability in the MDA-MB-231 breast cancer cell line. AVN-C has the most potent decrease in tumor cell viability, decreasing viable cells to below 25% at 400 µM when compared to control after 96 h. We demonstrate that treatment with AVN-C causes DNA fragmentation and accumulation of over 90% of cells into a sub G cell cycle population. Further, we conclude that AVN-C treated cells activate apoptosis because 97% of treated cells stain positive for annexin V while 91% have caspase-3/7 activity, a late marker of apoptosis.

CONCLUSIONS

Breast cancer cells treated with AVN-C have a decrease in cell viability, an increase in the sub G population, and stain positive for both annexin V and caspase activity, indicating that AVN-C induces apoptosis in breast cancer cells. These compounds may be able to act as chemotherapeutics as demonstrated through future in vivo studies.

摘要

背景

燕麦酰胺(AVN)是一类研究相对较少的植物化学物质,可能是新型的化学治疗剂。这些存在于燕麦中的化合物对健康细胞无毒,并且已显示在体外可降低人结肠癌和肝癌细胞的活力。然而,这些研究并未阐明单个燕麦酰胺的分子机制。在本研究中,我们旨在观察燕麦酰胺对MDA-MB-231乳腺癌细胞的影响。

方法

采用MTT法测定细胞活力。使用流式细胞仪进行染色和分析以确定细胞周期进程和细胞凋亡。使用FloJo软件分析流式细胞术数据。在所有实验中,通过双侧t检验确定统计学显著性。

结果

本研究表明,燕麦酰胺A、B和C分别降低MDA-MB-231乳腺癌细胞系的活力。燕麦酰胺C对肿瘤细胞活力的降低作用最强,在96小时后,与对照组相比,400µM时可将活细胞减少至25%以下。我们证明,用燕麦酰胺C处理会导致DNA片段化,并使超过90%的细胞积累到亚G期细胞周期群体中。此外,我们得出结论,经燕麦酰胺C处理的细胞激活了细胞凋亡,因为97%的处理细胞膜联蛋白V染色呈阳性,而91%具有半胱天冬酶-3/7活性,这是细胞凋亡的晚期标志物。

结论

用燕麦酰胺C处理的乳腺癌细胞活力降低,亚G期群体增加,膜联蛋白V和半胱天冬酶活性染色均呈阳性,表明燕麦酰胺C诱导乳腺癌细胞凋亡。这些化合物可能能够作为化学治疗剂,未来的体内研究将对此进行验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ac/5648482/530241b32ab4/12935_2017_464_Fig1_HTML.jpg

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