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首页> 外文OA文献 >(6E, 10E) Isopolycerasoidol and (6E, 10E) isopolycerasoidol methyl ester, prenylated benzopyran derivatives from pseuduvaria monticola induce mitochondrial-mediated apoptosis in human breast adenocarcinoma cells
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(6E, 10E) Isopolycerasoidol and (6E, 10E) isopolycerasoidol methyl ester, prenylated benzopyran derivatives from pseuduvaria monticola induce mitochondrial-mediated apoptosis in human breast adenocarcinoma cells

机译：（6E，10E）异聚芥子醇和（6E，10E）异聚芥子醇甲酯，假单胞菌假单胞菌的烯丙基化苯并吡喃衍生物诱导线粒体介导的人乳腺癌细胞凋亡

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Phytochemicals from Pseuduvaria species have been reported to display a wide range of biological activities. In the present study, a known benzopyran derivative, (6E, 10E) isopolycerasoidol (1), and a new benzopyran derivative, (6E, 10E) isopolycerasoidol methyl ester (2), were isolated from a methanol extract of Pseuduvaria monticola leaves. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR, IR, UV, and LCMS-QTOF, and by comparison with previously published data. The anti-proliferative and cytotoxic effects of these compounds on human breast cancer cell-lines (MCF-7 and MDA-MB-231) and a human normal breast epithelial cell line (MCF-10A) were investigated. MTT results revealed both (1) and (2) were efficient in reducing cell viability of breast cancer cells. Flow cytometry analysis demonstrated that (1) and (2) induced cell death via apoptosis, as demonstrated by an increase in phosphotidylserine exposure. Both compounds elevated ROS production, leading to reduced mitochondrial membrane potential and increased plasma membrane permeability in breast cancer cells. These effects occurred concomitantly with a dose-dependent activation of caspase 3/7 and 9, a down-regulation of the anti-apoptotic gene BCL2 and the accumulation of p38 MAPK in the nucleus. Taken together, our data demonstrate that (1) and (2) induce intrinsic mitochondrial- mediated apoptosis in human breast cancer cells, which provides the first pharmacological evidence for their future development as anticancer agents.
机译：据报道，假单胞菌属物种的植物化学物质具有广泛的生物活性。在本研究中，从Pseuduvaria monticola叶的甲醇提取物中分离出一种已知的苯并吡喃衍生物（6E，10E）异聚芥酸（1）和一种新的苯并吡喃衍生物（6E，10E）异聚芥酸甲酯（2）。通过光谱方法（包括1D和2D NMR，IR，UV和LCMS-QTOF）阐明了分离的化合物的结构，并与以前发表的数据进行了比较。研究了这些化合物对人乳腺癌细胞系（MCF-7和MDA-MB-231）和人正常乳腺癌上皮细胞系（MCF-10A）的抗增殖和细胞毒性作用。 MTT结果显示（1）和（2）均可有效降低乳腺癌细胞的细胞活力。流式细胞仪分析表明（1）和（2）通过凋亡诱导细胞死亡，如磷脂酰丝氨酸暴露的增加所证明。两种化合物均提高了ROS的产生，导致线粒体膜电位降低，并增加了乳腺癌细胞的质膜通透性。这些作用与caspase 3/7和9的剂量依赖性激活，抗凋亡基因BCL2的下调以及p38 MAPK在细胞核中的积累同时发生。两者合计，我们的数据表明（1）和（2）诱导人乳腺癌细胞内在的线粒体介导的凋亡，这为它们作为抗癌药的未来发展提供了第一个药理证据。

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