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没食子酸和姜黄素可诱导人乳腺癌细胞MDA-MB-231产生细胞毒性并引发凋亡。

Gallic acid and curcumin induce cytotoxicity and apoptosis in human breast cancer cell MDA-MB-231.

作者信息

Moghtaderi Hassan, Sepehri Houri, Delphi Ladan, Attari Farnoosh

机构信息

Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

出版信息

Bioimpacts. 2018;8(3):185-194. doi: 10.15171/bi.2018.21. Epub 2018 Mar 5.

Abstract

Gallic acid (GA) and curcumin (Cur) are natural phenolic compounds that their anti-tumor effects on many types of cancers have been proved. In the current study, the effect of the combination of these agents on MDA-MB-231 breast cancer cells was investigated. Inhibition of cell proliferation (MTT assay), light microscopy, fluorescence microscopy, cell cycle analysis, nitrite detection, ROS levels, measurement of the mitochondrial membrane potential, GSH level, Annexin V assay, RT-PCR and Western blotting methods were applied. The results revealed the combination of GA and Cur strongly decreased MDA-MB-231 cell growth. Moreover, this combination increased ROS level and cytotoxic activity along with the glutathione depletion in MDA-MB-231 cells. Flow cytometry analysis showed the combination of GA and Cur increased sub-G1 cell population. Furthermore, fluorescent staining and Annexin V/PI assay showed that apoptotic cells were significantly increased in the presence of GA and Cur. At last, protein expression evaluation showed that the combination of GA and Cur significantly decreased Bcl-2 level while increased Bax, cleaved-caspase3 and PARP levels in MDA-MB-231 cells. These results suggest that GA in combination with Cur could be a possible candidate for chemoprevention agent of triple negative breast cancer.

摘要

没食子酸(GA)和姜黄素(Cur)是天然酚类化合物,它们对多种癌症的抗肿瘤作用已得到证实。在本研究中,研究了这些药物联合使用对MDA-MB-231乳腺癌细胞的影响。应用细胞增殖抑制(MTT法)、光学显微镜、荧光显微镜、细胞周期分析、亚硝酸盐检测、活性氧水平、线粒体膜电位测量、谷胱甘肽水平、膜联蛋白V检测、逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹法。结果显示,GA和Cur联合使用可显著降低MDA-MB-231细胞的生长。此外,这种联合使用还增加了MDA-MB-231细胞中的活性氧水平和细胞毒性活性,同时消耗了谷胱甘肽。流式细胞术分析表明,GA和Cur联合使用增加了亚G1期细胞群体。此外,荧光染色和膜联蛋白V/碘化丙啶(PI)检测表明,在GA和Cur存在的情况下,凋亡细胞显著增加。最后,蛋白质表达评估显示,GA和Cur联合使用显著降低了MDA-MB-231细胞中的Bcl-2水平,同时增加了Bax、裂解的半胱天冬酶3和聚(ADP-核糖)聚合酶(PARP)的水平。这些结果表明,GA与Cur联合使用可能是三阴性乳腺癌化学预防剂的一个潜在候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854c/6128975/c0139f4d9c9c/bi-8-185-g001.jpg

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