G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Pr. 100-letya Vladivostoka 159, 690022 Vladivostok, Russia.
Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Road, Sanmin District, Kaohsiung City 80708, Taiwan.
Mar Drugs. 2024 Oct 17;22(10):474. doi: 10.3390/md22100474.
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 A-1 (Cuc A-1) and djakonovioside A (Dj A), isolated from the sea cucumber . 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 A-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 A-1 and djakonovioside A activate the intrinsic apoptotic pathway in triple-negative breast cancer cells. Additionally, it was found that treatment with Cuc A-1 resulted in in vivo inhibition of tumor growth and metastasis of murine solid Ehrlich adenocarcinoma.
乳腺癌是全球女性最常见的癌症类型。三阴性乳腺癌对患者最为不利，但对化疗最为敏感。海参三萜糖苷具有作为抗癌药物的高治疗潜力。本研究旨在鉴定从海参中分离出的糖苷 cucumarioside A-1 (Cuc A-1) 和 djakonovioside A 触发和调节 MDA-MB-231 细胞（三阴性乳腺癌细胞系）的途径。使用流式细胞术、荧光显微镜、免疫印迹和 ELISA 研究了化合物在微摩尔浓度下对细胞周期停滞、凋亡诱导、活性氧 (ROS) 水平、线粒体膜电位 (Δψm) 和抗凋亡和促凋亡蛋白表达的影响。糖苷导致 MDA-MB-231 细胞周期停滞，刺激 ROS 产生增加，Δψm 降低。Cucumarioside A-1 和 djakonovioside A 引起的线粒体膜去极化导致 APAF-1 和细胞色素 C 水平增加。这反过来又导致 caspase-9 和 caspase-3 的激活以及其裂解形式的水平增加。糖苷还影响与 MDA-MB-231 细胞中线粒体介导的凋亡相关的 Bax 和 Bcl-2 蛋白的表达。这些结果表明，Cuc A-1 和 djakonovioside A 激活三阴性乳腺癌细胞中的内在凋亡途径。此外，还发现 Cuc A-1 的治疗导致小鼠实体 Ehrlich 腺癌的肿瘤生长和转移的体内抑制。
