{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T18:04:26Z","timestamp":1779818666705,"version":"3.53.1"},"reference-count":100,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Breast cancer (BC) has a highly aggressive and metastatic nature. Specifically, triple-negative breast cancer (TNBC) is highly complicated to treat and recover from. Nowadays, treatment strategies focus on the beneficial nature of the herbal source.\n                    <jats:italic>Otostegia fruticosa<\/jats:italic>\n                    gained focus on treating various cancers due to its potential against cancer. This study aimed to investigate the apoptotic and metastasis properties of\n                    <jats:italic>Otostegia fruticosa<\/jats:italic>\n                    against triple-negative breast cancer cells (MDA-MB-231). The ethanol extract of\n                    <jats:italic>Otostegia fruticosa<\/jats:italic>\n                    exhibited cytotoxic effect on MDA-MB-231 cells, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 23 \u00b5g\/mL. various tests, including MTT, morphological analysis, fluorescence staining, and Trypan blue exclusion, invasion, migration ability were employed to evaluate the effects of\n                    <jats:italic>Otostegia fruticosa<\/jats:italic>\n                    on cell viability and apoptosis. The results showed that\n                    <jats:italic>Otostegia fruticosa<\/jats:italic>\n                    induced apoptosis in MDA-MB-231 cells, characterized by the accumulation of reactive oxygen species (ROS), mitochondrial damage, and loss of nuclear potential. Furthermore,\n                    <jats:italic>Otostegia fruticosa<\/jats:italic>\n                    treatment reduced cell viability due to excessive ROS generation, as evidenced by DCFH-DA staining. Functional assays revealed that\n                    <jats:italic>Otostegia fruticosa<\/jats:italic>\n                    impaired cellular mobility, invasion, and colony-forming ability in MDA-MB-231 cells. The\n                    <jats:italic>Otostegia fruticose<\/jats:italic>\n                    significantly suppresses invasion property of breast cancer cells about 50% and significantly reduced migrated cells time dependent manner. Gene expression analysis by qRT-PCR and immunofluorescence showed altered expressions of genes linked to apoptotic (Caspase-3, 8, 9, and Bcl2, Bax, Bid, Cytochrome c, PTEN) and metastasis (MMP-9) protein. Notably,\n                    <jats:italic>Otostegia fruticosa<\/jats:italic>\n                    downregulated MMP9 and OPN protein expressions, while upregulating caspase-9 and Cyt-c. Western blot analysis validated these findings, highlighting the involvement of the p-Akt and OPN downregulation. Altogether, this study demonstrates that\n                    <jats:italic>Otostegia fruticosa<\/jats:italic>\n                    induces apoptosis and inhibits metastasis in MDA-MB-231 cells by regulating caspase-3, 8, and 9, Bcl2, Bax, and Bid. Meanwhile, it potentially arrests the translation level of MMP-9 and OPN proteins. In addition, cellular migration and invasion were significantly downregulated, and\n                    <jats:italic>Otostegia fruticosa<\/jats:italic>\n                    possesses the anti-tumor effect against the TNBC cells (MDA-MB-231).\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0349314","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:28:52Z","timestamp":1779816532000},"page":"e0349314","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ethanolic extract of Otostegia fruticosa induces ROS-dependent apoptosis and reduces migration of MDA-MB-231 cells in vitro"],"prefix":"10.1371","volume":"21","author":[{"given":"Abdulrahman","family":"Alasmari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chellasamy","family":"Panneerselvam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1480-3555","authenticated-orcid":true,"given":"Saravanan","family":"Muthupandian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7244-2172","authenticated-orcid":true,"given":"Goyitom","family":"Gebremedhn Gebru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"issue":"17","key":"pone.0349314.ref001","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.3390\/cancers13174287","article-title":"Breast cancer-epidemiology, risk factors, classification, prognostic markers, and current treatment strategies-an updated review","volume":"13","author":"S \u0141ukasiewicz","year":"2021","journal-title":"Cancers (Basel)"},{"key":"pone.0349314.ref002","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":"F Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"pone.0349314.ref003","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13058-020-01296-5","article-title":"Triple-negative breast cancer molecular subtyping and treatment progress","volume":"22","author":"L Yin","year":"2020","journal-title":"Breast Cancer Res"},{"issue":"2","key":"pone.0349314.ref004","first-page":"162","article-title":"ERalpha-negative and triple negative breast cancer: molecular features and potential therapeutic approaches","volume":"1796","author":"J-Q Chen","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"pone.0349314.ref005","article-title":"Triple negative breast cancer - an overview","author":"K Aysola","year":"2013","journal-title":"Hered Genet Curr Res"},{"issue":"9","key":"pone.0349314.ref006","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1351\/pac199971091611","article-title":"Novel strategies for the discovery of plant-derived anticancer agents","volume":"71","author":"AD Kinghorn","year":"1999","journal-title":"Pure Appl Chem"},{"key":"pone.0349314.ref007","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/1388020039051744","article-title":"Novel strategies for the discovery of plant-derived anticancer agents","volume":"41","author":"A Kinghorn","year":"2003","journal-title":"Pharm Biol"},{"key":"pone.0349314.ref008","first-page":"102189","article-title":"Otostegia fruticosa (Forssk.) - A comprehensive insight of its ethnopharmacology, phytochemistry, and pharmacological activities","volume":"32","author":"MF Hawwal","year":"2024","journal-title":"Saudi Pharm J SPJ Off Publ Saudi Pharm Soc"},{"key":"pone.0349314.ref009","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1055\/a-0953-6165","article-title":"A review of the phytochemistry, traditional uses, and biological activities of the Genus Ballota and Otostegia","volume":"85","author":"S Rosselli","year":"2019","journal-title":"Planta Med"},{"issue":"16","key":"pone.0349314.ref010","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1080\/14786419.2022.2130306","article-title":"A new firewall in the fight against breast cancer: in-vitro and in-silico studies correlating chemistry to apoptotic activity of Otostegia fruticosa","volume":"37","author":"SA Al-Madhagy","year":"2023","journal-title":"Nat Prod Res"},{"key":"pone.0349314.ref011","first-page":"175","article-title":"Activity of Otostegia fruticosa (Lamiaceae) leaves extracts against lymphatic filariasis vector, Culex pipiens L. 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