{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T21:17:28Z","timestamp":1787779048092,"version":"build-2784847793"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Itraconazole (ITRA) is a broad-spectrum antifungal agent approved by the Food and Drug Administration (FDA). It has been shown to inhibit cancer growth, but the underlying molecular mechanism of itraconazole-induced cell death in acute myeloid leukemia (AML) remains largely elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CCK-8 assay, colony-formation assay, flow cytometry, Western blotting, reactive oxygen species (ROS) detection, and ferroptosis analysis were performed to reveal the role and underlying mechanisms of itraconazole in AML cell lines. Itraconazole has also done research on\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Itraconazole significantly inhibits the viability of AML cell lines and arrests the cell cycle at the G2\/M phase. Further investigations reveal that itraconazole effectively induces ferroptosis in AML cells, as evidenced by iron dependency and mitochondrial dysfunction. Notably, the TP53INP1 signaling pathway is markedly upregulated in itraconazole-treated AML cells. Knockdown of TP53INP1 significantly attenuates itraconazole-induced ferroptosis by regulating iron metabolism, which in turn restores mitochondrial function and elevates SLC7A11 and GPX4 levels. Meanwhile,\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments demonstrate that itraconazole impairs AML progression. It is worth noting that concomitant changes in apoptotic markers were also observed, suggesting that itraconazole may simultaneously trigger both apoptotic and ferroptotic pathways, which may coexist in AML cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that itraconazole exerts anti-leukemic effects associated with ferroptosis induction involving TP53INP1, though apoptosis may coexist, supporting its further evaluation as a therapeutic candidate for AML.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1890539","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:18:43Z","timestamp":1787775523000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Itraconazole induced ferroptosis in acute myeloid leukemia cells through TP53INP1"],"prefix":"10.3389","volume":"13","author":[{"given":"Yan","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Hematology, Daping Hospital, Third Military Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhao","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Hematology, Daping Hospital, Third Military Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hematology, Daping Hospital, Third Military Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shidi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Hematology, Daping Hospital, Third Military Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanting","family":"She","sequence":"additional","affiliation":[{"name":"Department of Hematology, Daping Hospital, Third Military Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Daping Hospital, Third Military Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Hematology, Daping Hospital, Third Military Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Weapon Bioeffect Assessment, Research Institute of Surgery, Third Military Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Hematology, Daping Hospital, Third Military Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11120685","article-title":"Repurposing itraconazole loaded PLGA nanoparticles for improved antitumor efficacy in non-small cell lung cancers","volume":"11","author":"Alhakamy","year":"2019","journal-title":"Pharmaceutics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1111\/j.1365-2141.1976.tb03563.x","article-title":"Proposals for the classification of the acute leukaemias. french-american-british (FAB) co-operative group","volume":"33","author":"Bennett","year":"1976","journal-title":"Br. 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