{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:22:02Z","timestamp":1787559722097,"version":"build-2736575974"},"reference-count":100,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"Scientific and Technological Research Council of T\u00fcrkiye","doi-asserted-by":"publisher","award":["324S179"],"award-info":[{"award-number":["324S179"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"award":["324S179"],"award-info":[{"award-number":["324S179"]}],"id":[{"id":"https:\/\/ror.org\/04w9kkr77","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Drug repurposing represents an accelerated and cost-effective approach to discovering novel oncologic therapeutics. Here, we investigated the anticancer potential and underlying mechanisms of marbofloxacin (MBF), a veterinary fluoroquinolone (FQ), against breast cancer (BC) cells. Methods: The cellular impacts of MBF on cell viability, anchorage-dependent growth, tumorigenicity, migration, apoptosis, proliferation, senescence, and mitochondrial function were thoroughly characterized. To further elucidate its mechanistic activity, real-time qRT-PCR, untargeted LC-MS\/MS-based metabolomics, network pharmacology, and molecular docking analysis were integrated. Results: MBF suppressed BC cell growth by inhibiting cellular proliferation and migration, disrupting mitochondrial membrane potential, and inducing ROS-mediated apoptosis and irreversible cellular senescence. These phenotypic impacts were accompanied by upregulation of tumor suppressors such as CDKN1A and PUMA and downregulation of oncogenes including MKI67, BIRC5, and BCL-2. Metabolomic analysis revealed broad suppression of biosynthesis-related metabolic pathways, characterized by the depletion of critical polyamines and nucleotide pathways. Network pharmacology and molecular docking analyses identified EGFR and HSP90AA1 as putative hub proteins potentially associated with the observed anticancer phenotype. Conclusions: These results provide initial evidence that MBF induces metabolic and molecular rewiring in BC, highlighting its promise as a repositionable therapeutic candidate.<\/jats:p>","DOI":"10.3390\/ph19091327","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:03:41Z","timestamp":1787558621000},"page":"1327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Marbofloxacin Suppresses Breast Cancer Growth Through Oxidative Stress and Metabolic Reprogramming with Predicted HSP90AA1\u2013EGFR Network Modulation"],"prefix":"10.3390","volume":"19","author":[{"given":"Mervenur","family":"Yavuz","sequence":"first","affiliation":[{"name":"Molecular Biology and Genetics Program, Institute of Natural Sciences, Mugla Sitki Kocman University, Mugla 48000, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7813-8435","authenticated-orcid":false,"given":"Firli R. P.","family":"Dewi","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya 60115, Indonesia"},{"name":"Research Center for Stem Cells Development, Universitas Airlangga, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130lknur","family":"Keskin","sequence":"additional","affiliation":[{"name":"Histology and Embryology Department, School of Medicine, \u0130stanbul Medipol University, \u0130stanbul 34810, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Turan","family":"Demircan","sequence":"additional","affiliation":[{"name":"Medical Biology Department, School of Medicine, \u0130zmir Bakircay University, \u0130zmir 35665, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","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. 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