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分析鉴定加味四君子汤中对 MCF-7 人乳腺癌细胞有毒性的活性化合物。

Analysis and Identification of Active Compounds from Gami-Soyosan Toxic to MCF-7 Human Breast Adenocarcinoma Cells.

机构信息

Department of Obstetrics and Gynecology, College of Korean Medicine, Daejeon University, Daejeon 35235, Korea.

Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.

出版信息

Biomolecules. 2019 Jul 10;9(7):272. doi: 10.3390/biom9070272.

Abstract

Gami-soyosan is a medicinal herbal formulation prescribed for the treatment of menopausal symptoms, including hot flashes and osteoporosis. Gami-soyosan is also used to treat similar symptoms experienced by patients with breast cancer. The incidence of breast cancer in women receiving hormone replacement therapy is a big burden. However, little is known about the components and their mechanism of action that exhibit these beneficial effects of Gami-soyosan. The aim of this study was to simultaneously analyze compounds of Gami-soyosan, and determine their cytotoxic effects on estrogen receptor (ER)-positive MCF-7 human breast adenocarcinoma cells. We established a simultaneous analysis method of 18 compounds contained in Gami-soyosan and found that, among the various compounds in Gami-soyosan, gallic acid (), decursin (), and decursinol angelate () suppressed the viability of MCF-7 cells. Gallic acid (), decursin (), and decursinol angelate () induced apoptotic cell death and significantly increased poly (ADP-ribose) polymerase (PARP) cleavage and the Bcl-2-associated X protein/ B-cell lymphoma 2 (Bax/Bcl-2) ratio. Decursin () increased the expression of cleaved caspases-8, -9, -7, and -3. Decursinol angelate () increased the expression of cleaved caspase-8 and -7. These three components altered the different apoptosis signal pathways. Collectively, gallic acid (), decursin (), and decursinol angelate () may be used to inhibit cell proliferation synergistically in patients with ER-positive breast cancer.

摘要

甘味逍遥散是一种用于治疗更年期症状(包括热潮红和骨质疏松症)的草药配方,也用于治疗乳腺癌患者类似的症状。接受激素替代疗法的女性乳腺癌发病率是一个沉重的负担。然而,对于表现出甘味逍遥散这些有益作用的成分及其作用机制知之甚少。本研究的目的是同时分析甘味逍遥散中的化合物,并确定它们对雌激素受体(ER)阳性 MCF-7 人乳腺癌腺癌细胞的细胞毒性作用。我们建立了一种同时分析甘味逍遥散中 18 种化合物的方法,发现甘味逍遥散中的各种化合物中,没食子酸()、当归酸()和当归醇当归酸酯()抑制 MCF-7 细胞活力。没食子酸()、当归酸()和当归醇当归酸酯()诱导细胞凋亡死亡,并显著增加多聚(ADP-核糖)聚合酶(PARP)裂解和 Bcl-2 相关 X 蛋白/ B 细胞淋巴瘤 2(Bax/Bcl-2)比值。当归酸()增加了裂解半胱天冬酶-8、-9、-7 和 -3 的表达。当归醇当归酸酯()增加了裂解半胱天冬酶-8 和 -7 的表达。这三种成分改变了不同的凋亡信号通路。总之,没食子酸()、当归酸()和当归醇当归酸酯()可能协同用于抑制 ER 阳性乳腺癌患者的细胞增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4324/6681368/0bfd315978f4/biomolecules-09-00272-g002a.jpg

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