{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:05:13Z","timestamp":1789963513801,"version":"4.0.1"},"reference-count":85,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515220221"],"award-info":[{"award-number":["2023A1515220221"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["202211003"],"award-info":[{"award-number":["202211003"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Breast cancer (BC) is a leading cause of cancer\u2010related mortality worldwide. Ferroptosis is a non\u2010apoptotic regulated cell death that has been linked to the progression of BC and represents a promising therapeutic target for this malignancy. Baicalin (BA) is recognized for its antioxidant, anticancer, and anti\u2010inflammatory effect. Although the ferroptosis\u2010mediated antitumor activity of BA has been widely demonstrated in various cancers, its potential to induce ferroptosis in BC remains unclear. To explore its regulation of ferroptosis in BC and identify the underlying mechanisms, we performed multi\u2010dimensional experiments to investigate the mechanisms of BA\u2010induced ferroptosis. Proliferatively, CCK\u20108 and colony formation assays were employed to measure the viability and reproductive capacity of cells, complemented by a nude mouse xenograft model for in\u00a0vivo validation. Subsequently, we demonstrated BA\u2010induced cell death via ferroptosis in\u00a0vitro and in\u00a0vivo in BC, accompanied by ROS and lipid peroxidation accumulation, GSH depletion, intracellular liable Fe\n                    <jats:sup>2+<\/jats:sup>\n                    enrichment and mitochondrial damage. Notably, these effects were reversed by ferrostatin\u20101. The pan\u2010caspase inhibitor Z\u2010VAD\u2010FMK and Fer\u20101 rescued BA\u2010induced cell death, whereas necroptosis inhibitors necrosulfonamide and necroptosis inhibitor necrostatin\u20101 as well as autophagy inhibitor chloroquine did not exert such effects. Significantly, ferroptosis serves as the predominant cell death mechanism. Mechanistically, we performed network pharmacology analysis and molecular docking to explore the interaction between BA and STAT3\/HO\u20101\/GPX4. Functionally, BA effectively disrupted GPX4\u2010dependent ferroptosis defense and induced BC cell death. As a natural compound modulating this ferroptosis\u2010related axis, BA is a promising therapeutic alternative to conventional chemotherapy, which is limited by severe systemic toxicity. Collectively, this work reveals BA may regulate ferroptosis via the potential STAT3\/HO\u20101\/GPX4 signaling axis.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70426","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:30:18Z","timestamp":1789961418000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Baicalin Induces Ferroptosis in Breast Cancer Through a Novel\n                    <scp>STAT3<\/scp>\n                    \/\n                    <scp>HO<\/scp>\n                    \u20101\/\n                    <scp>GPX4<\/scp>\n                    Regulatory Axis"],"prefix":"10.1002","author":[{"given":"Tingting","family":"Guo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment\/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of 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Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1527-8174","authenticated-orcid":false,"given":"Alicia Marcelina D\u00edaz","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Bioinorganic Laboratory, Department of General and Inorganic Chemistry, Faculty of Chemistry University of Havana  Havana Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1910-9615","authenticated-orcid":false,"given":"Mulazim Hussain","family":"Asim","sequence":"additional","affiliation":[{"name":"College of Pharmacy University of Sargodha  Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen Traditional Chinese Medicine Hospital  Shenzhen 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