{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:26:08Z","timestamp":1791689168197,"version":"4.3.4"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100016114","name":"Zhejiang Medical Association","doi-asserted-by":"publisher","award":["YS2024-50-010"],"award-info":[{"award-number":["YS2024-50-010"]}],"id":[{"id":"10.13039\/501100016114","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017531","name":"Medical and Health Research Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2024KY1497"],"award-info":[{"award-number":["2024KY1497"]}],"id":[{"id":"10.13039\/501100017531","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1016\/j.phymed.2025.156912","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T20:15:54Z","timestamp":1748636154000},"page":"156912","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"special_numbering":"C","title":["Brusatol induced ferroptosis in osteosarcoma cells by modulating the Keap1\/Nrf2\/SLC7A11 signaling pathway"],"prefix":"10.1016","volume":"144","author":[{"given":"Long","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doudou","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijiang","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijiao","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"13","key":"10.1016\/j.phymed.2025.156912_bib0001","doi-asserted-by":"crossref","DOI":"10.1128\/MCB.00099-20","article-title":"The molecular mechanisms regulating the KEAP1-NRF2 pathway","volume":"40","author":"Baird","year":"2020","journal-title":"Mol. Cell Biol."},{"issue":"5","key":"10.1016\/j.phymed.2025.156912_bib0002","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.bbamcr.2018.02.010","article-title":"Nrf2-Keap1 signaling in oxidative and reductive stress","volume":"1865","author":"Bellezza","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"10.1016\/j.phymed.2025.156912_bib0003","series-title":"Intermolecular Forces: Proceedings of the Fourteenth Jerusalem Symposium on Quantum Chemistry and Biochemistry Held in Jerusalem, Israel, April 13\u201316, 1981","first-page":"331","article-title":"Interaction models for water in relation to protein hydration","author":"Berendsen","year":"1981"},{"key":"10.1016\/j.phymed.2025.156912_bib0004","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2022.122379","article-title":"A liposomal formulation of simvastatin and doxorubicin for improved cardioprotective and anti-cancer effect","volume":"629","author":"Bj\u00f8rnstad","year":"2022","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.phymed.2025.156912_bib0005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2020.12.024","article-title":"Immunotherapy for osteosarcoma: fundamental mechanism, rationale, and recent breakthroughs","volume":"500","author":"Chen","year":"2021","journal-title":"Cancer Lett."},{"key":"10.1016\/j.phymed.2025.156912_bib0006","article-title":"Keap1-Nrf2 pathway: a key mechanism in the occurrence and development of cancer","volume":"14","author":"Chen","year":"2024","journal-title":"Front. Oncol."},{"issue":"5","key":"10.1016\/j.phymed.2025.156912_bib0007","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/s41571-020-00462-0","article-title":"Broadening horizons: the role of ferroptosis in cancer","volume":"18","author":"Chen","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.phymed.2025.156912_bib0008","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2022.154323","article-title":"Brusatol suppresses the growth of intrahepatic cholangiocarcinoma by PI3K\/Akt pathway","volume":"104","author":"Chen","year":"2022","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2025.156912_bib0009","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.775680","article-title":"Brusatol inhibits proliferation and invasion of glioblastoma by down-regulating the expression of ECM1","volume":"12","author":"Dai","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.phymed.2025.156912_bib0010","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2023.155282","article-title":"Mangiferin attenuates osteoporosis by inhibiting osteoblastic ferroptosis through Keap1\/Nrf2\/SLC7A11\/GPX4 pathway","volume":"124","author":"Deng","year":"2024","journal-title":"Phytomedicine"},{"issue":"1","key":"10.1016\/j.phymed.2025.156912_bib0011","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1186\/s12967-021-03042-7","article-title":"SLC7A11 regulated by NRF2 modulates esophageal squamous cell carcinoma radiosensitivity by inhibiting ferroptosis","volume":"19","author":"Feng","year":"2021","journal-title":"J. Transl. Med."},{"issue":"10","key":"10.1016\/j.phymed.2025.156912_bib0012","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/s41571-021-00519-8","article-title":"Advancing therapy for osteosarcoma","volume":"18","author":"Gill","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"issue":"13","key":"10.1016\/j.phymed.2025.156912_bib0013","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21134777","article-title":"NRF2, a transcription factor for stress response and beyond","volume":"21","author":"He","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"3","key":"10.1016\/j.phymed.2025.156912_bib0014","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/prot.21123","article-title":"Comparison of multiple Amber force fields and development of improved protein backbone parameters","volume":"65","author":"Hornak","year":"2006","journal-title":"Proteins."},{"issue":"13","key":"10.1016\/j.phymed.2025.156912_bib0015","doi-asserted-by":"crossref","first-page":"5877","DOI":"10.7150\/thno.73714","article-title":"Single-cell transcriptomics reveals the regulative roles of cancer associated fibroblasts in tumor immune microenvironment of recurrent osteosarcoma","volume":"12","author":"Huang","year":"2022","journal-title":"Theranostics."},{"issue":"1","key":"10.1016\/j.phymed.2025.156912_bib0016","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s12943-023-01804-z","article-title":"Exosome-mediated miR-144-3p promotes ferroptosis to inhibit osteosarcoma proliferation, migration, and invasion through regulating ZEB1","volume":"22","author":"Jiang","year":"2023","journal-title":"Mol. Cancer"},{"issue":"4","key":"10.1016\/j.phymed.2025.156912_bib0017","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: mechanisms, biology and role in disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"7","key":"10.1016\/j.phymed.2025.156912_bib0018","doi-asserted-by":"crossref","first-page":"10327","DOI":"10.1021\/acsnano.2c00192","article-title":"Mitochondria-targeting polymer micelle of dichloroacetate induced pyroptosis to enhance osteosarcoma immunotherapy","volume":"16","author":"Jin","year":"2022","journal-title":"ACS. Nano"},{"issue":"4","key":"10.1016\/j.phymed.2025.156912_bib0019","doi-asserted-by":"crossref","DOI":"10.3390\/cells12040659","article-title":"Doxorubicin-an agent with multiple mechanisms of anticancer activity","volume":"12","author":"Kciuk","year":"2023","journal-title":"Cells"},{"issue":"8","key":"10.1016\/j.phymed.2025.156912_bib0020","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s13238-020-00789-5","article-title":"Cystine transporter SLC7A11\/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy","volume":"12","author":"Koppula","year":"2021","journal-title":"Protein Cell"},{"issue":"1","key":"10.1016\/j.phymed.2025.156912_bib0021","doi-asserted-by":"crossref","first-page":"74","DOI":"10.7150\/ijbs.33787","article-title":"Metformin induces cell cycle arrest, apoptosis and autophagy through ROS\/JNK signaling pathway in human osteosarcoma","volume":"16","author":"Li","year":"2020","journal-title":"Int. J. Biol. Sci."},{"issue":"12","key":"10.1016\/j.phymed.2025.156912_bib0022","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1016\/j.molcel.2022.03.022","article-title":"Ferroptosis at the intersection of lipid metabolism and cellular signaling","volume":"82","author":"Liang","year":"2022","journal-title":"Mol. Cell"},{"key":"10.1016\/j.phymed.2025.156912_bib0023","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.111202","article-title":"EF24 induces ferroptosis in osteosarcoma cells through HMOX1","volume":"136","author":"Lin","year":"2021","journal-title":"Biomed. PharmacOther"},{"key":"10.1016\/j.phymed.2025.156912_bib0024","unstructured":"Lu T. Sobtop [Available from: http:\/\/sobereva.com\/soft\/Sobtop (accessed on December 5, 2024)."},{"issue":"2","key":"10.1016\/j.phymed.2025.156912_bib0025","doi-asserted-by":"crossref","DOI":"10.3390\/antib11020040","article-title":"Discovering novel small molecule compound for prevention of monoclonal antibody self-association","volume":"11","author":"Lui","year":"2022","journal-title":"Antibodies"},{"issue":"22","key":"10.1016\/j.phymed.2025.156912_bib0026","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1056\/NEJMra2103423","article-title":"New Horizons in the treatment of osteosarcoma","volume":"385","author":"Meltzer","year":"2021","journal-title":"N. Engl. J. Med."},{"issue":"1","key":"10.1016\/j.phymed.2025.156912_bib0027","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13045-019-0720-y","article-title":"Ferroptosis, a new form of cell death: opportunities and challenges in cancer","volume":"12","author":"Mou","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.phymed.2025.156912_bib0028","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2023.176009","article-title":"Butyrate enhances erastin-induced ferroptosis of osteosarcoma cells via regulating ATF3\/SLC7A11 pathway","volume":"957","author":"Nie","year":"2023","journal-title":"Eur. J. Pharmacol."},{"issue":"11","key":"10.1016\/j.phymed.2025.156912_bib0029","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.trecan.2022.06.009","article-title":"Drug independence and the curability of cancer by combination chemotherapy","volume":"8","author":"Pomeroy","year":"2022","journal-title":"Trends. Cancer"},{"issue":"Suppl 7","key":"10.1016\/j.phymed.2025.156912_bib0030","doi-asserted-by":"crossref","first-page":"vii320","DOI":"10.1093\/annonc\/mdq276","article-title":"Osteosarcoma","volume":"21","author":"Ritter","year":"2010","journal-title":"Ann. Oncol."},{"issue":"1","key":"10.1016\/j.phymed.2025.156912_bib0031","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0245358","article-title":"Insights into structure and dynamics of extracellular domain of toll-like receptor 5 in Cirrhinus mrigala (mrigala): A molecular dynamics simulation approach","volume":"16","author":"Rout","year":"2021","journal-title":"PLoS. One"},{"issue":"2","key":"10.1016\/j.phymed.2025.156912_bib0032","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/bph.15713","article-title":"Osteosarcoma mechanobiology and therapeutic targets","volume":"179","author":"Shoaib","year":"2022","journal-title":"Br. J. Pharmacol."},{"issue":"7","key":"10.1016\/j.phymed.2025.156912_bib0033","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/j.drudis.2016.05.015","article-title":"Drug combination therapy increases successful drug repositioning","volume":"21","author":"Sun","year":"2016","journal-title":"Drug Discov. Today"},{"issue":"8","key":"10.1016\/j.phymed.2025.156912_bib0034","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2022.e10410","article-title":"The Nrf2 inhibitor brusatol synergistically enhances the cytotoxic effect of lapatinib in HER2-positive cancers","volume":"8","author":"Tian","year":"2022","journal-title":"Heliyon"},{"key":"10.1016\/j.phymed.2025.156912_bib0035","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.arr.2015.04.002","article-title":"Programmed cell death in aging","volume":"23","author":"Tower","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.phymed.2025.156912_bib0036","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2023.154881","article-title":"Baicalin induces ferroptosis in osteosarcomas through a novel Nrf2\/xCT\/GPX4 regulatory axis","volume":"116","author":"Wen","year":"2023","journal-title":"Phytomedicine"},{"issue":"6","key":"10.1016\/j.phymed.2025.156912_bib0037","first-page":"1123","article-title":"Osteosarcoma: a multidisciplinary approach to diagnosis and treatment","volume":"65","author":"Wittig","year":"2002","journal-title":"Am. Fam. Physician"},{"issue":"7","key":"10.1016\/j.phymed.2025.156912_bib0038","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1093\/jpp\/rgae017","article-title":"Brusatol's anticancer activity and its molecular mechanism: a research update","volume":"76","author":"Xi","year":"2024","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.phymed.2025.156912_bib0039","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2021.152680","article-title":"Apoptotic activities of brusatol in human non-small cell lung cancer cells: involvement of ROS-mediated mitochondrial-dependent pathway and inhibition of Nrf2-mediated antioxidant response","volume":"451","author":"Xie","year":"2021","journal-title":"Toxicology."},{"issue":"3","key":"10.1016\/j.phymed.2025.156912_bib0040","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1152\/physrev.00023.2017","article-title":"The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis","volume":"98","author":"Yamamoto","year":"2018","journal-title":"Physiol. Rev."},{"issue":"1","key":"10.1016\/j.phymed.2025.156912_bib0041","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cmet.2022.09.021","article-title":"Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy","volume":"35","author":"Yang","year":"2023","journal-title":"Cell Metab."},{"issue":"4","key":"10.1016\/j.phymed.2025.156912_bib0042","first-page":"359","article-title":"Brusatol: A potential anti-tumor quassinoid from Brucea javanica","volume":"12","author":"Yu","year":"2020","journal-title":"Chin. Herb. Med."},{"key":"10.1016\/j.phymed.2025.156912_bib0043","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2025.156464","article-title":"Brusatol inhibits malignant phenotypes and lipid metabolism of osteosarcoma cells by regulating PI3K\/AKT and MAPK pathways","volume":"139","author":"Yuan","year":"2025","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2025.156912_bib0044","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.117094","article-title":"Penfluridol regulates p62 \/Keap1 \/ Nrf2 signaling pathway to induce ferroptosis in osteosarcoma cells","volume":"177","author":"Zeng","year":"2024","journal-title":"Biomed. PharmacOther"},{"key":"10.1016\/j.phymed.2025.156912_bib0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2024.103066","article-title":"Hydrogen sulfide protects cardiomyocytes from doxorubicin-induced ferroptosis through the SLC7A11\/GSH\/GPx4 pathway by Keap1 S-sulfhydration and Nrf2 activation","volume":"70","author":"Zhang","year":"2024","journal-title":"Redox. Biol."},{"key":"10.1016\/j.phymed.2025.156912_bib0046","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.115567","article-title":"Brusatol induces ferroptosis in oesophageal squamous cell carcinoma by repressing GSH synthesis and increasing the labile iron pool via inhibition of the NRF2 pathway","volume":"167","author":"Zhu","year":"2023","journal-title":"Biomed. PharmacOther"},{"issue":"3","key":"10.1016\/j.phymed.2025.156912_bib0047","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711325005501?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711325005501?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T21:58:08Z","timestamp":1750283888000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711325005501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":47,"alternative-id":["S0944711325005501"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2025.156912","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Brusatol induced ferroptosis in osteosarcoma cells by modulating the Keap1\/Nrf2\/SLC7A11 signaling pathway","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2025.156912","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier GmbH. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"156912"}}