海参三萜苷 Cucumarioside A0-1 和 Djakonovioside A 对人类三阴性乳腺癌的作用机制。

IF 4.9 2区 医学 Q1 CHEMISTRY, MEDICINAL
Marine Drugs Pub Date : 2024-10-17 DOI:10.3390/md22100474
Ekaterina S Menchinskaya, Ekaterina A Chingizova, Evgeny A Pislyagin, Ekaterina A Yurchenko, Anna A Klimovich, Elena A Zelepuga, Dmitry L Aminin, Sergey A Avilov, Alexandra S Silchenko
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引用次数: 0

摘要

乳腺癌是全球妇女最常见的癌症。三阴性乳腺癌对患者最不利,但也对化疗最敏感。海参中的三萜苷类化合物具有很高的抗癌治疗潜力。本研究旨在确定从海参 Cucumaria djakonovi 中分离出来的苷类物质 cucumarioside A0-1(Cuc A0-1)和 djakonovioside A(Dj A)在 MDA-MB-231 细胞(三阴性乳腺癌细胞系)中触发和调节的途径。利用流式细胞仪、荧光显微镜、免疫印迹法和酶联免疫吸附法,研究了微摩尔浓度的化合物对细胞周期停滞、细胞凋亡诱导、活性氧(ROS)水平、线粒体膜电位(Δψm)以及抗凋亡蛋白和促凋亡蛋白表达的影响。在 MDA-MB-231 细胞中,苷类导致细胞周期停滞,刺激 ROS 生成增加,并降低Δψm。葫芦皂甙 A0-1 和 djakonovioside A 引起的线粒体膜去极化导致 APAF-1 和细胞色素 C 水平升高,进而激活了 caspase-9 和 caspase-3,并增加了其裂解形式的水平。苷还会影响 Bax 和 Bcl-2 蛋白的表达,这两种蛋白与 MDA-MB-231 细胞线粒体介导的细胞凋亡有关。这些结果表明,葫芦苷 A0-1 和苦绳甙 A 能激活三阴性乳腺癌细胞的内在凋亡途径。此外,研究还发现 Cuc A0-1 还能抑制小鼠实体艾氏腺癌的体内生长和转移。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mechanisms of Action of Sea Cucumber Triterpene Glycosides Cucumarioside A0-1 and Djakonovioside A Against Human Triple-Negative Breast Cancer.

Breast cancer is the most prevalent form of cancer in women worldwide. Triple-negative breast cancer is the most unfavorable for patients, but it is also the most sensitive to chemotherapy. Triterpene glycosides from sea cucumbers possess a high therapeutic potential as anticancer agents. This study aimed to identify the pathways triggered and regulated in MDA-MB-231 cells (triple-negative breast cancer cell line) by the glycosides cucumarioside A0-1 (Cuc A0-1) and djakonovioside A (Dj A), isolated from the sea cucumber Cucumaria djakonovi. Using flow cytometry, fluorescence microscopy, immunoblotting, and ELISA, the effects of micromolar concentrations of the compounds on cell cycle arrest, induction of apoptosis, the level of reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), and expression of anti- and pro-apoptotic proteins were investigated. The glycosides caused cell cycle arrest, stimulated an increase in ROS production, and decreased Δψm in MDA-MB-231 cells. The depolarization of the mitochondrial membrane caused by cucumarioside A0-1 and djakonovioside A led to an increase in the levels of APAF-1 and cytochrome C. This, in turn, resulted in the activation of caspase-9 and caspase-3 and an increase in the level of their cleaved forms. Glycosides also affected the expression of Bax and Bcl-2 proteins, which are associated with mitochondria-mediated apoptosis in MDA-MB-231 cells. These results indicate that cucumarioside A0-1 and djakonovioside A activate the intrinsic apoptotic pathway in triple-negative breast cancer cells. Additionally, it was found that treatment with Cuc A0-1 resulted in in vivo inhibition of tumor growth and metastasis of murine solid Ehrlich adenocarcinoma.

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来源期刊
Marine Drugs
Marine Drugs 医学-医药化学
CiteScore
9.60
自引率
14.80%
发文量
671
审稿时长
1 months
期刊介绍: Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.
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