{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:47:22Z","timestamp":1792133242281,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008003","name":"Korea Institute of Radiological and Medical Sciences","doi-asserted-by":"publisher","award":["50531\u20102026"],"award-info":[{"award-number":["50531\u20102026"]}],"id":[{"id":"10.13039\/501100008003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102025\u201000553853"],"award-info":[{"award-number":["RS\u20102025\u201000553853"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp;amp; Perspec"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ferroptosis, an iron\u2010dependent form of regulated cell death driven by excessive lipid peroxidation, has emerged as a promising therapeutic strategy for cancer. Metformin, a widely used biguanide antidiabetic drug, has recently been reported to induce ferroptosis and exert anticancer effects in various malignancies. However, metformin or its analogue phenformin did not induce ferroptotic cell death in H1299 non\u2010small cell lung cancer cells and HEYA8 ovarian cancer cells for up to 24\u2009h. Instead, both drugs attenuated cysteine deprivation\u2010induced ferroptotic cell death, which also appeared to involve necroptotic signaling. This effect was accompanied by reductions in reactive oxygen species generation, iron accumulation, and lipid peroxidation at both the cellular and mitochondrial levels. Notably, metformin and phenformin suppressed cysteine deprivation\u2010induced mitochondrial membrane hyperpolarization and increased oxygen consumption, suggesting suppression of mitochondrial bioenergetic activity associated with cysteine deprivation\u2010induced ferroptosis. Cysteine deprivation markedly reduced glutathione (GSH) levels and glutathione peroxidase 4 (GPX4) expression. Although metformin alone also reduced intracellular GSH levels, metformin did not restore GSH levels or GPX4 expression under cysteine deprivation despite suppressing ferroptosis, indicating that its anti\u2010ferroptotic effects are independent of the canonical GSH\u2010GPX4 axis. Collectively, these findings underscore that the use of biguanides should be carefully considered when applying cysteine deprivation\u2010based ferroptosis\u2010inducing strategies in cancer.<\/jats:p>","DOI":"10.1002\/prp2.70330","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:27:34Z","timestamp":1791437254000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin Inhibits Ferroptotic Cell Death by Suppressing Cysteine Deprivation\u2010Induced Mitochondrial Dysfunction"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5444-7161","authenticated-orcid":false,"given":"Se\u2010Kyeong","family":"Jang","sequence":"first","affiliation":[{"name":"Division of Radiation Biomedical Research Korea Institute of Radiological and Medical Sciences  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selim","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Radiation Biomedical Research Korea Institute of Radiological and Medical Sciences  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4133-6032","authenticated-orcid":false,"given":"Gyeongmi","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Radiation Biomedical Research Korea Institute of Radiological and Medical Sciences  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3878-6059","authenticated-orcid":false,"given":"Jungil","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology, College of Science and Convergence Technology Seoul Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u2010Chul","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Radiation Biomedical Research Korea Institute of Radiological and Medical Sciences  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1144-5991","authenticated-orcid":false,"given":"Hyeon\u2010Ok","family":"Jin","sequence":"additional","affiliation":[{"name":"KIRAMS Radiation Biobank Korea Institute of Radiological and Medical Sciences  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.10.042"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00459-0"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.09.068"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-00462-0"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.04.002"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.12.001"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.89"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2018.11.001"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-02208-x"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-021-00271-y"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00642-w"},{"issue":"2","key":"e_1_2_13_14_1","first-page":"84","article-title":"How Erastin Assassinates Cells by Ferroptosis Revealed","volume":"14","author":"Gan B.","year":"2023","journal-title":"Protein & Cell"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7237"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.11.039"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4336-x"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4372-6"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-023-00833-4"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-023-02655-6"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-02012-7"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmaa180"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-023-08492-4"},{"issue":"5","key":"e_1_2_13_24_1","first-page":"3119","article-title":"Induction of HSP27 and HSP70 by Constitutive Overexpression of Redd1 Confers Resistance of Lung Cancer Cells to Ionizing Radiation","volume":"41","author":"Jin H. 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