{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:26:25Z","timestamp":1791260785179,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-14-00100"],"award-info":[{"award-number":["25-14-00100"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Triple-negative breast cancer (TNBC) represents significant therapeutic challenges due to its aggressive behavior, metabolic plasticity, and lack of targeted treatments, prompting investigation of biologically active triterpene glycosides from the starfish Solaster pacificus. This study evaluated the ability of pacificusoside D (SpD) to synergistically enhance the anticancer efficacy of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) in TNBC MDA-MB-231 cells by targeting mitochondrial oxidative phosphorylation (OXPHOS). Methods included metabolic profiling via glucose uptake, lactate, and glutamate Glo assays; IC50 determination by MTS and trypan blue assays; colony formation evaluation using a soft agar assay; and molecular mechanism elucidation by Western blot, fluorescence microscopy and spectrometry, and flow cytometry analyses. Results demonstrated that MDA-MB-231 cells predominantly utilized glycolysis under basal conditions, shifting to OXPHOS with 2-DG (0.5 mM). IC50 values were 8.0\/8.4 mM for 2-DG and 0.3\/0.25 \u03bcM for SpD after 24 h of cell treatment. SpD exhibited a significant decrease in the number of colonies in MDA-MB-231 cells and possessed synergistic anticancer effects with 2-DG. Mechanistically, SpD increased tumor suppressor VHL expression level, down-regulated expression level of electron transport chain enzymes, generated reactive oxygen species, induced mitochondrial dysfunction, and triggered Bax\/Bak-mediated apoptosis. These findings highlighted the synergistic anticancer potential of SpD in combination with 2-DG in aggressive breast cancer, offering insights into improved clinical outcomes in the future.<\/jats:p>","DOI":"10.3390\/md24020075","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:28:11Z","timestamp":1770910091000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Anticancer Effect of Pacificusoside D from the Starfish Solaster pacificus in Combination with 2-Deoxy-D-glucose on Oxidative Phosphorylation in Triple-Negative Breast Cancer Cells MDA-MB-231"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3262-0373","authenticated-orcid":false,"given":"Olesya S.","family":"Malyarenko","sequence":"first","affiliation":[{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 100-let Vladivostok Ave., Vladivostok 690022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6594-8471","authenticated-orcid":false,"given":"Timofey V.","family":"Malyarenko","sequence":"additional","affiliation":[{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 100-let Vladivostok Ave., Vladivostok 690022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1371-0103","authenticated-orcid":false,"given":"Alla A.","family":"Kicha","sequence":"additional","affiliation":[{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 100-let Vladivostok Ave., Vladivostok 690022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana P.","family":"Ermakova","sequence":"additional","affiliation":[{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 100-let Vladivostok Ave., Vladivostok 690022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9075-8584","authenticated-orcid":false,"given":"Natalia V.","family":"Ivanchina","sequence":"additional","affiliation":[{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 100-let Vladivostok Ave., Vladivostok 690022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, August 14). Breast Cancer. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/breast-cancer."},{"key":"ref_2","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Carvalho, E., Canberk, S., Schmitt, F., and Vale, N. (2025). Molecular subtypes and mechanisms of breast cancer: Precision medicine approaches for targeted therapies. 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