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
{"title":"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。","authors":"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","doi":"10.3390/md22100474","DOIUrl":null,"url":null,"abstract":"<p><p>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<sub>0</sub>-1 (Cuc A<sub>0</sub>-1) and djakonovioside A (Dj A), isolated from the sea cucumber <i>Cucumaria djakonovi</i>. 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<sub>0</sub>-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<sub>0</sub>-1 and djakonovioside A activate the intrinsic apoptotic pathway in triple-negative breast cancer cells. Additionally, it was found that treatment with Cuc A<sub>0</sub>-1 resulted in in vivo inhibition of tumor growth and metastasis of murine solid Ehrlich adenocarcinoma.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509090/pdf/","citationCount":"0","resultStr":"{\"title\":\"Mechanisms of Action of Sea Cucumber Triterpene Glycosides Cucumarioside A<sub>0</sub>-1 and Djakonovioside A Against Human Triple-Negative Breast Cancer.\",\"authors\":\"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\",\"doi\":\"10.3390/md22100474\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sub>0</sub>-1 (Cuc A<sub>0</sub>-1) and djakonovioside A (Dj A), isolated from the sea cucumber <i>Cucumaria djakonovi</i>. 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<sub>0</sub>-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<sub>0</sub>-1 and djakonovioside A activate the intrinsic apoptotic pathway in triple-negative breast cancer cells. Additionally, it was found that treatment with Cuc A<sub>0</sub>-1 resulted in in vivo inhibition of tumor growth and metastasis of murine solid Ehrlich adenocarcinoma.</p>\",\"PeriodicalId\":18222,\"journal\":{\"name\":\"Marine Drugs\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-10-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509090/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Marine Drugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/md22100474\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Marine Drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/md22100474","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
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.
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.