连翘叶三萜通过线粒体途径诱导乳腺癌细胞凋亡

IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY
Xiao Li, Xuefang Wang, Ling Chen, Erjuan Ning, Hang Fan, Jun Liang, Xinxin Lai, Lulu Zhang, Yingkui Gao, Yan Li, Panpeng Wei, Liqin Yu, Yi Fan, Xuebing Wang
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引用次数: 0

摘要

连翘是一种中药。悬浮莲的叶子,特别是这种植物的干叶子,在中国通常被当作茶食用。本研究从悬钩子叶中分离纯化了悬钩子叶三萜(FLT),并对其体外抗肿瘤活性及相关分子机制进行了系统的研究。首先,采用高效液相色谱法测定其主要成分,结果表明熊果酸(70.67%)、齐墩果酸(16.23%)和白桦酸(4.59%)为其主要成分。接下来,3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)实验结果显示,FLT对人乳腺癌MCF-7和MDA-MB-231细胞具有很强的抗增殖活性(p < 0.05)。此外,使用Annexin v -荧光素异硫氰酸酯/碘化丙啶(Annexin V-FITC/PI)进行细胞凋亡的流式细胞术检测显示,FLT显著诱导MCF-7和MDA-MB-231细胞凋亡,且呈剂量依赖性(p < 0.001)。激光共聚焦显微镜显示,FLT主要位于细胞的线粒体和溶酶体中。同时,15 μg/mL FLT处理MCF-7和MDA-MB-231细胞后,线粒体膜电位(MMP) (p < 0.001)和细胞内活性氧(ROS)水平(p < 0.001)均显著降低。最后,western blotting显示,FLT(10和15 μg/mL)显著降低b细胞淋巴瘤-2 (Bcl-2) (p < 0.001)和天冬氨酸半胱氨酸特异性蛋白酶-3 (caspase-3)蛋白水平(p < 0.001),但显著升高Bcl-2同源拮抗剂/杀伤剂(Bak)蛋白(p <; 0.05或p <; 0.001)、切割-caspase-3蛋白(p < 0.001)、动态相关蛋白1 (DRP1)和线粒体裂变1蛋白(FIS1)水平(p <; 0.01或p <; 0.001)。综上所述,FLT通过激活线粒体通路促进MCF-7和MDA-MB-231细胞的凋亡。这种作用可能是由于FLT通过促进DRP1和fis1介导的线粒体分裂,从而激活caspase-3的裂解,最终导致细胞凋亡,从而影响线粒体中Bcl-2家族的表达。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Forsythia suspensa Leaves Triterpenoids Induce Breast Cancer Cell Apoptosis via the Mitochondrial Pathway

Forsythia suspensa Leaves Triterpenoids Induce Breast Cancer Cell Apoptosis via the Mitochondrial Pathway

Forsythia suspensa is a traditional Chinese medicine. The leaves of F. suspensa, specifically the dried leaves of the plant, are commonly consumed as tea in China. In this study, F. suspensa leaves triterpenoids (FLT) were isolated and purified from the dried leaves of F. suspensa, and their in vitro antitumor activity as well as associated molecular mechanisms were systematically investigated. First, the primary components of FLT were determined using high-performance liquid chromatography (HPLC), and the results revealed ursolic acid (70.67%), oleanolic acid (16.23%), and betulinic acid (4.59%) as the major components. Next, the results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that FLT exhibited strong antiproliferative activity (p < 0.05) toward human breast cancer MCF-7 and MDA-MB-231 cells. Moreover, the flow cytometry detection of apoptosis using Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) revealed that FLT significantly induced apoptosis in MCF-7 and MDA-MB-231 cells in a dose-dependent manner (p < 0.001). Laser confocal microscopy showed that FLT was mainly located in the mitochondria and lysosome of cells. Meanwhile, after the FLT (15 μg/mL) treatment of MCF-7 and MDA-MB-231 cells, the mitochondrial membrane potential (MMP) (p < 0.001) and intracellular reactive oxygen species (ROS) level (p < 0.001) were significantly reduced. Finally, western blotting demonstrated that FLT (10 and 15 μg/mL) significantly reduced B-cell lymphoma-2 (Bcl-2) (p < 0.001) and cysteinyl aspartate specific proteinase-3 (caspase-3) protein levels (p < 0.001), but significantly increased Bcl-2 homologous antagonist/killer (Bak) protein (p < 0.05 or p < 0.001), cleaved-caspase-3 protein (p < 0.001), dynamic-related protein 1 (DRP1), and mitochondrial fission 1 protein (FIS1) levels (p < 0.01 or p < 0.001). Taken together, the results indicated that FLT promoted the apoptosis of MCF-7 and MDA-MB-231 cells by activating the mitochondrial pathway. This effect may be attributed to FLT affecting the expression of the Bcl-2 family in mitochondria by promoting DRP1 and FIS1-mediated mitochondrial division, thereby activating the cleavage of caspase-3 and ultimately leading to cell apoptosis.

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来源期刊
Food Science & Nutrition
Food Science & Nutrition Agricultural and Biological Sciences-Food Science
CiteScore
7.40
自引率
5.10%
发文量
434
审稿时长
24 weeks
期刊介绍: Food Science & Nutrition is the peer-reviewed journal for rapid dissemination of research in all areas of food science and nutrition. The Journal will consider submissions of quality papers describing the results of fundamental and applied research related to all aspects of human food and nutrition, as well as interdisciplinary research that spans these two fields.
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