{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:58:29Z","timestamp":1785437909199,"version":"3.56.0"},"reference-count":46,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research and Development Project of Sichuan Science and Technology Department","award":["024YFFK0379"],"award-info":[{"award-number":["024YFFK0379"]}]},{"award":["024YFFK0379"],"award-info":[{"award-number":["024YFFK0379"]}],"id":[{"id":"https:\/\/ror.org\/04323m874","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2024NSFSC1720"],"award-info":[{"award-number":["2024NSFSC1720"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2024NSFSC1720"],"award-info":[{"award-number":["2024NSFSC1720"]}],"id":[{"id":"https:\/\/ror.org\/04323m874","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Uveal melanoma (UM) represents an uncommon intraocular malignancy with high aggressiveness. Dysregulation of ferroptosis has been associated with UM progression. Dihydroartemisinin (DHA), a natural derivative of Artemisia annua, exhibits potent antitumor activity with a favorable safety profile, yet its role in ferroptosis regulation in UM remains unclear. Here, we showed that DHA significantly reduced the proliferation and invasiveness of UM cells\u2014both primary and secondary\u2014with effects intensifying over time and dose. Transcriptomic analysis indicated that DHA may exert antitumor effects by modulating the ferroptosis-related pathway, characterized by upregulating heme oxygenase-1 (HO-1) and downregulating the SLC7A11 (xCT)\/GPX4 axis, leading to iron accumulation, increased ROS and lipid peroxidation, and mitochondrial dysfunction. Iron chelators and pancaspase inhibitors partially reverse these effects, whereas HO-1 inducers enhance them. Overall, our results suggest that DHA suppresses UM progression by inducing ferroptosis and mitochondrial dysfunction, while the HO-1 and xCT\/GPX4 pathways may contribute to these effects. DHA may represent a potential therapeutic approach for UM, warranting further investigation.<\/jats:p>","DOI":"10.3390\/ijms27073027","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T15:10:24Z","timestamp":1774537824000},"page":"3027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dihydroartemisinin Induces Ferroptosis in Uveal Melanoma Cells Through the HO-1 and xCT\/GPX4 Signaling Pathways"],"prefix":"10.3390","volume":"27","author":[{"given":"Yuxuan","family":"Zhao","sequence":"first","affiliation":[{"name":"Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7378-2195","authenticated-orcid":false,"given":"Lirong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longqian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3547-3436","authenticated-orcid":false,"given":"Naihong","family":"Yan","sequence":"additional","affiliation":[{"name":"Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100060","DOI":"10.1016\/j.apjo.2024.100060","article-title":"Uveal Melanoma: Current Evidence on Prognosis, Treatment and Potential Developments","volume":"13","author":"Gelmi","year":"2024","journal-title":"Asia-Pac. 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