{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:19:04Z","timestamp":1790853544640,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["gyfynsfc\u20102022\u201025"],"award-info":[{"award-number":["gyfynsfc\u20102022\u201025"]}],"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":["82360493"],"award-info":[{"award-number":["82360493"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>New uses of old drugs hold great promise for clinical translation. Flubendazole, an FDA\u2010approved antiparasitic drug, has been shown to target p53 and promote apoptosis in glioblastoma (GBM) cells. However, its damaging mechanism in GBM remains elusive. Herein, we explored the ferroptosis\u2010inducing ability of flubendazole on GBM cells. After treating glioma cell lines U251 and LN229 with the flubendazole (DMSO &lt;1\u2030), cell viability was inhibited in a concentration\u2010dependent manner (IC<jats:sub>50<\/jats:sub> for LN229\u2009=\u20090.5331\u2009\u03bcM, IC<jats:sub>50<\/jats:sub> for U251\u2009=\u20090.6809\u2009\u03bcM), attributed to the induction of ferroptosis, as evidenced by increased MDA levels, accumulation of ROS and lipid peroxides, change in mitochondrial membrane potential and structure. Protein analysis related to ferroptosis showed upregulation of TFRC, DMT1 and p53, alongside downregulation of xCT, FHC and GPX4 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). All\u2010atom docking studies demonstrated that flubendazole bound closely with xCT, and TFRC, validating its role in inducing glioma ferroptosis via modulation of these proteins. Notably, flubendazole could damage the glioblastoma stem cells (GSC) that are typically resistant to other therapies, thereby possessing advantages in stopping glioma recurrence. This study delved into the mechanisms of flubendazole\u2010induced ferroptosis in glioma, broadening its application and providing new ideas for new uses of other old drugs.<\/jats:p>","DOI":"10.1111\/jcmm.70188","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T04:14:24Z","timestamp":1731644064000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Repurposing flubendazole for glioblastoma ferroptosis by affecting <scp>xCT<\/scp> and <scp>TFRC<\/scp> proteins"],"prefix":"10.1111","volume":"28","author":[{"given":"Wei","family":"Teng","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The Affiliated Hospital of Guizhou Medical University  Guiyang Guizhou China"},{"name":"Department of Clinical Medicine Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanguo","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Hospital of Guizhou Medical University  Guiyang Guizhou China"},{"name":"Department of Clinical Medicine Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niya","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Cen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Hospital of Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Hospital of Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Hospital of Guizhou Medical University  Guiyang Guizhou China"},{"name":"Department of Neurosurgery, Guizhou Provincial People's Hospital  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Hospital of Guizhou Medical University  Guiyang Guizhou China"},{"name":"Department of Clinical Medicine Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9765-5115","authenticated-orcid":false,"given":"Liangzhao","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Hospital of Guizhou Medical University  Guiyang Guizhou China"},{"name":"Department of Clinical Medicine Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.280319"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.73.0119"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-325334"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.324301.119"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-010-1123-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.10.010"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00324-8"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-00462-0"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00459-0"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.04.002"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14344"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105305"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.09.013"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abn1128"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-017-0017-2"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20193314"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2022.01.007"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026623666230623145802"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/d2ra02697j"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2012.06.006"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13956"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.07.013"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2584"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2015.10.014"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2015.158"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1303-z"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01530-y"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70188","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T14:21:45Z","timestamp":1733149305000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.70188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":27,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/jcmm.70188"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.70188","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-01-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70188"}}