{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:39:03Z","timestamp":1785425943792,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001459","name":"Ministry of Education","doi-asserted-by":"publisher","award":["0071-1446-S"],"award-info":[{"award-number":["0071-1446-S"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"award":["0071-1446-S"],"award-info":[{"award-number":["0071-1446-S"]}],"id":[{"id":"https:\/\/ror.org\/00q919b81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer is among the most commonly diagnosed malignancies in women and remains difficult to treat due to therapy resistance and the adverse effects associated with conventional chemotherapeutic regimens. In this study, the anticancer activity of the ethanolic root extract of Salvadora persica (S. persica), commonly known as Miswak, was evaluated in human breast cancer cells using a combination of in vitro assays, phytochemical profiling, and computational analyses. HRLC-MS\/MS characterization revealed a wide range of bioactive constituents, including alkaloids, flavonoid derivatives, glucosinolates, and fatty acid\u2013based molecules detected under both ionization modes. The extract exhibited a concentration-dependent cytotoxic effect on breast cancer MCF-7 and MDA-MB-231 cells, with IC50 values of 144.1 and 176.3 \u00b5g\/mL, respectively, as determined by the MTT assay, while exerting negligible toxicity toward normal Vero cells. Miswak extract enhanced intracellular ROS production, disruption of MMP, nuclear condensation, and increased apoptotic cell populations, along with S-phase cell cycle arrest, pointing toward activation of mitochondrial-mediated apoptosis. In silico docking results indicated that key phytoconstituents exhibit strong binding interactions with multiple breast cancer\u2013relevant targets such as ER\u03b1, PR, EGFR, HER3, IGF-1R, and GPER. Additionally, pharmacokinetic and toxicity predictions suggested favorable drug-like properties with minimal safety concerns. Thus, these findings support its potential as a promising plant-derived therapeutic candidate for breast cancer.<\/jats:p>","DOI":"10.3390\/ijms27135751","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:49:23Z","timestamp":1782434963000},"page":"5751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anticancer Activity of Miswak Root Extract in Breast Cancer Cell Line: HRLC-MS\/MS Profiling, In Vitro Evaluation, and In Silico Analysis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3956-1150","authenticated-orcid":false,"given":"Abrar","family":"Turki","sequence":"first","affiliation":[{"name":"Clinical Nutrition Department, College of Applied Medical Sciences, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6009-5222","authenticated-orcid":false,"given":"Md. Abul","family":"Barkat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3082-9368","authenticated-orcid":false,"given":"Yasmin Basheer","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Department, College of Applied Medical Sciences, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshita","family":"Barkat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghad Rashed","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khursheed","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Era\u2019s Lucknow Medical College and Hospital, Era University, Lucknow 226003, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumana","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Era\u2019s Lucknow Medical College and Hospital, Era University, Lucknow 226003, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-1465","authenticated-orcid":false,"given":"Sahabjada","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Era\u2019s Lucknow Medical College and Hospital, Era University, Lucknow 226003, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2147\/DDDT.S336643","article-title":"The role of progesterone receptors in breast cancer","volume":"16","author":"Li","year":"2022","journal-title":"Drug Des. 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