{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:43:47Z","timestamp":1783529027071,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82503400"],"award-info":[{"award-number":["82503400"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070676"],"award-info":[{"award-number":["32070676"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370683"],"award-info":[{"award-number":["32370683"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025M78355"],"award-info":[{"award-number":["2025M78355"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515010737 2023A1515012902"],"award-info":[{"award-number":["2021A1515010737 2023A1515012902"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Triple\u2010negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. Here, we identify xanthatin, a sesquiterpene lactone from Xanthium species, as a potent inhibitor of TNBC cell growth with minimal toxicity to normal cells. Transcriptomic analyses revealed that xanthatin activates ferroptosis, evidenced by elevated ROS, lipid peroxidation, and Fe\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    accumulation, together with GSH depletion and downregulation of SLC7A11 and GPX4. Target identification by drug affinity responsive target stability and mass spectrometry uncovered CDGSH iron sulfur domain 1 (CISD1) as the direct binding partner of xanthatin. Cellular thermal shift assay, surface plasmon resonance, and dynamics simulations consistently demonstrated that tryptophan\u201075 is the critical residue mediating this interaction. Functionally, xanthatin promotes CISD1 ubiquitination and proteasomal degradation, thereby disrupting mitochondrial iron homeostasis and inducing ferroptosis. CISD1 destabilization further impaired mitochondrial integrity and activated PINK1\/Parkin\u2010dependent mitophagy, establishing a dual ferroptosis\u2013mitophagy mechanism. Importantly, genetic knockdown of CISD1 markedly attenuated the anticancer activity of xanthatin, confirming its essential role. In an orthotopic TNBC mouse model, xanthatin significantly suppressed tumor growth without causing systemic toxicity. Collectively, our findings provide the first demonstration that xanthatin directly targets CISD1 at the Trp\u201075 site to trigger ferroptosis and mitophagy, highlighting its promise as a therapeutic candidate for TNBC.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520051","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T10:45:48Z","timestamp":1770374748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Xanthatin Targets CISD1 to Drive Ferroptosis and Mitophagy as a Dual Anticancer Strategy in Triple\u2010Negative Breast Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Qinwen","family":"Liu","sequence":"first","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease Zhujiang Hospital Southern Medical University  Guangzhou P. R. China"},{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University  Guangzhou P. R. China"},{"name":"Institute of Systems Medicine and Health Sciences School of Chinese Medicine Hong Kong Baptist University  Hong Kong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenshen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfeng","family":"Du","sequence":"additional","affiliation":[{"name":"Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine For Qingzhi Diseases  Guangzhou P. R. China"},{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou Guangdong P. R. China"},{"name":"Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine Southern Medical University  Guangzhou Guangdong P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Systems Medicine and Health Sciences School of Chinese Medicine Hong Kong Baptist University  Hong Kong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1414-0189","authenticated-orcid":false,"given":"Daogang","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles Southern Medical University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60534"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.66"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-3045"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2202809"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443404"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177772"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010019\u20100318\u20105"},{"key":"e_1_2_14_10_1","first-page":"2025","article-title":"Xanthatin induces apoptosis through ROS\u2010mediated c\u2010FLIP inhibition in human retinoblastoma","volume":"12","author":"Gao X.","year":"2025","journal-title":"cells"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules17043736"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C700107200"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2014.05.001"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S388537"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2025.14981"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.09.003"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2014.10.014"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u201000324\u20108"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010024\u201000701\u20103"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094\u2010023\u201003136\u20102"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.97027"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202413174"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010020\u20102730\u20107"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21941"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2018.10.041"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.1041"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2025.107902"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010025\u201007710\u20100"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031665"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202520051","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202520051","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202520051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T19:09:33Z","timestamp":1776193773000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202520051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":28,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/advs.202520051"],"URL":"https:\/\/doi.org\/10.1002\/advs.202520051","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]},"assertion":[{"value":"2025-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e20051"}}