{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:23:48Z","timestamp":1777512228930,"version":"3.51.4"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Arts and Sciences Dean\u2019s Office"},{"name":"University Research Board (URB) of the American University of Beirut, Lebanon"},{"name":"University of Petra, Amman, Jordan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with poor prognosis and limited targeted therapeutic options. Natural products, rich in bioactive phytochemicals, represent a potential source of novel anticancer agents. This study examined the phytochemical profile and anticancer activity of an ethanolic bulb extract of Cyclamen persicum (CPE), with a primary focus on TNBC. Methods: The phytochemical composition of CPE was analyzed by liquid chromatography\u2013mass spectrometry (LC\u2013MS). Antioxidant activity was evaluated using DPPH radical scavenging assay. The anticancer effects of CPE were assessed mainly in MDA-MB-231 TNBC cells using MTT cell viability assays, Ki-67 immunoblotting, Western blot analysis of signaling proteins, wound healing migration assays, Matrigel invasion assays, adhesion assays and cell\u2013cell aggregation assays. Antiproliferative activity was also examined in 22RV1 (prostate), Capan-2 (pancreatic), and HCT116 (intestinal) cancer cell lines using MTT assays. Results: LC\u2013MS analysis indicated that the extract contains multiple polyphenolic and organic acid constituents commonly associated with bioactivity. Consistent with this profile, CPE demonstrated strong antioxidant activity. In MDA-MB-231 cells, CPE significantly reduced cell viability and proliferation, accompanied by decreased Ki-67 expression. Treatment was associated with modulation of proteins involved in proliferative and survival signaling, induction of apoptosis-related markers, and reduced migratory and invasive capacities. CPE also promoted cell\u2013cell homotypic aggregation, suggesting a shift toward a less aggressive phenotype. These effects were associated with reduced phosphorylation of p65, indicating possible modulation of NF-\u03baB signaling. Additionally, CPE decreased proliferation in 22RV1, Capan-2, and HCT116 cancer cell lines. Conclusions: Collectively, these findings indicate that C. persicum bulb extract exerts multimodal anticancer effects in vitro, particularly in TNBC cells, and highlights its potential as a source of bioactive compounds warranting further mechanistic and translational investigation.<\/jats:p>","DOI":"10.3390\/ph19030388","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:06:59Z","timestamp":1772467619000},"page":"388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cyclamen persicum Bulb Extract Modulates NF-\u03baB, Oxidative Stress, and Apoptotic Pathways in Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"19","author":[{"given":"Aya","family":"Sharara","sequence":"first","affiliation":[{"name":"Department of Biology, American University of Beirut, Beirut P.O. Box 110236, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8183-7555","authenticated-orcid":false,"given":"Rola","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Department of Biology, American University of Beirut, Beirut P.O. Box 110236, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adnan","family":"Badran","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Jordan, Amman P.O. Box 11942, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9517-071X","authenticated-orcid":false,"given":"Rami A.","family":"Abdel-Rahem","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Petra, Amman P.O. Box 961343, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayyas","family":"Al-Remawi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, University of Petra, Amman P.O. Box 961343, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serine","family":"Baydoun","sequence":"additional","affiliation":[{"name":"Breast Imaging Section, Imaging Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3585-4765","authenticated-orcid":false,"given":"Marc","family":"Maresca","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, CNRS, Centrale Marseille, iSM2, 13013 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5632-1175","authenticated-orcid":false,"given":"Elias","family":"Baydoun","sequence":"additional","affiliation":[{"name":"Department of Biology, American University of Beirut, Beirut P.O. Box 110236, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","first-page":"151","article-title":"Epidemiological characteristics of and risk factors for breast cancer in the world","volume":"11","author":"Momenimovahed","year":"2019","journal-title":"Breast Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106535","DOI":"10.1016\/j.intimp.2020.106535","article-title":"Breast cancer: Biology, biomarkers, and treatments","volume":"84","author":"Barzaman","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"\u0141ukasiewicz, S., Czeczelewski, M., Forma, A., Baj, J., Sitarz, R., and Stanis\u0142awek, A. (2021). Breast Cancer-Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies-An Updated Review. 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