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Arvanil is a synthetic capsaicin derivative with favorable pharmacokinetic properties. This study showed that Arvanil enhances the anti-tumor effect of cisplatin in cisplatin-resistant ovarian cancer cells, partly associated with HMOX1-related ferroptosis. The combination treatment elevated reactive oxygen species (ROS), lipid peroxidation (LPO), and ferrous ion (Fe\u00b2\u207a) levels, suppressed GPX4 protein expression, and activated multiple key ferroptosis regulators. Inhibition of HMOX1 partially reversed these effects, confirming its pivotal regulatory role. In vivo experiments further validated the synergistic anti-tumor efficacy of the Arvanil-cisplatin combination, with no significant changes in body weight and no apparent histopathological or serum biochemical abnormalities detected under the tested conditions. This study provides a novel strategy to overcome cisplatin resistance and expands the potential application of small-molecule ferroptosis inducers in cancer therapy.<\/jats:p>","DOI":"10.1038\/s41598-026-51046-4","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T03:25:13Z","timestamp":1777692313000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Arvanil reverses cisplatin resistance in ovarian cancer by activating HMOX1-driven ferroptosis"],"prefix":"10.1038","volume":"16","author":[{"given":"Zhongping","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuojie","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangying","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"51046_CR1","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1038\/s43018-023-00617-9","volume":"4","author":"PA Konstantinopoulos","year":"2023","unstructured":"Konstantinopoulos, P. 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