{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:49:45Z","timestamp":1785408585022,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"crossref","award":["DS 37"],"award-info":[{"award-number":["DS 37"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"crossref","award":["DS 706"],"award-info":[{"award-number":["DS 706"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"crossref"}]},{"award":["DS 37"],"award-info":[{"award-number":["DS 37"]}],"id":[{"id":"https:\/\/ror.org\/016f61126","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DS 706"],"award-info":[{"award-number":["DS 706"]}],"id":[{"id":"https:\/\/ror.org\/016f61126","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Metastasis remains the leading cause of mortality in breast cancer and is closely linked to epithelial\u2013mesenchymal transition (EMT) and tumor microenvironment (TME)-associated processes. Diosmetin (DT), the active metabolite of diosmin, a widely used venoactive drug, has emerged as a potential anticancer agent. Building on our previous findings demonstrating that DT enhances doxorubicin efficacy, this study investigated its effects on tumor cell plasticity and stromal activation-associated responses. EMT was induced in MCF-7 cells, while a stromal model was established by TGF-\u03b2-mediated activation of BJ fibroblasts toward a cancer-associated fibroblast (CAF)-like phenotype. Additionally, doxorubicin-induced senescence was generated in fibroblasts. Migration assays and quantitative real-time PCR were used to assess functional and transcriptional changes. EMT induction resulted in decreased CDH1 expression and increased levels of VIM, MMP2, MMP9, IL-6, and HIF-1A, accompanied by enhanced migratory activity. DT attenuated TGF-\u03b2-induced CAF-like activation, as reflected by reduced expression of ACTA2, HGF, MMP2, MMP9, and IL6, and modulated hyaluronan turnover-related genes. Moreover, DT partially alleviated selected senescence-associated features in doxorubicin-treated fibroblasts. Collectively, these findings indicate that DT modulates EMT-associated plasticity and stromal activation-related responses in parallel in vitro models. Given its origin as a metabolite of a clinically used compound and its previously demonstrated chemosensitizing properties, DT may warrant further investigation as a potential adjunctive agent to modulate tumor- and stromal-associated processes in breast cancer.<\/jats:p>","DOI":"10.3390\/molecules31122111","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:46:28Z","timestamp":1781588788000},"page":"2111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diosmetin Modulates EMT-Associated Plasticity and Fibroblast-Activation Markers in Parallel Breast Cancer In Vitro Models"],"prefix":"10.3390","volume":"31","author":[{"given":"Monika","family":"Michalczyk","sequence":"first","affiliation":[{"name":"Doctoral School, Medical University of Lublin, 7 Chodzki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2766-3870","authenticated-orcid":false,"given":"Joanna","family":"Kubik","sequence":"additional","affiliation":[{"name":"Independent Medical Biology Unit, Faculty of Pharmacy, Medical University of Lublin, 8b Jaczewskiego Street, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-4692","authenticated-orcid":false,"given":"Aleksandra","family":"J\u00f3zefczyk","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy with Medicinal Plants Garden, Faculty of Pharmacy, Medical University of Lublin, 1 Chodzki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7834-0828","authenticated-orcid":false,"given":"Magdalena","family":"Iwan","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 6 Chodzki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4356-0828","authenticated-orcid":false,"given":"Ewelina","family":"Humeniuk","sequence":"additional","affiliation":[{"name":"Independent Medical Biology Unit, Faculty of Pharmacy, Medical University of Lublin, 8b Jaczewskiego Street, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1677-7247","authenticated-orcid":false,"given":"Grzegorz","family":"Adamczuk","sequence":"additional","affiliation":[{"name":"Department of Physiology and Toxicology, Institute of Medical Science, Faculty of Medicine, John Paul II Catholic University of Lublin, 1H Konstantynow, 20-708 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariola","family":"Michalczuk","sequence":"additional","affiliation":[{"name":"Independent Medical Biology Unit, Faculty of Pharmacy, Medical University of Lublin, 8b Jaczewskiego Street, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2165-9651","authenticated-orcid":false,"given":"Barbara","family":"Madej-Czerwonka","sequence":"additional","affiliation":[{"name":"Human Anatomy Department, Faculty of Medicine, Medical University of Lublin, 4 Jaczewskiego Street, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8007-5982","authenticated-orcid":false,"given":"Maciej","family":"Czerwonka","sequence":"additional","affiliation":[{"name":"Department of General, Oncological, Gastroenterological and Transplant Surgery, University Hospital in Krakow, Jagiellonian University, 2 Jakubowski Street, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-9681","authenticated-orcid":false,"given":"Agnieszka","family":"Korga-Plewko","sequence":"additional","affiliation":[{"name":"Independent Medical Biology Unit, Faculty of Pharmacy, Medical University of Lublin, 8b Jaczewskiego Street, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Feldo, M., W\u00f3jciak-Kosior, M., Sowa, I., Kocki, J., Bogucki, J., Zubilewicz, T., K\u0119sik, J., and Bogucka-Kocka, A. 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