{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:25:20Z","timestamp":1792553120669,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The treatment of prostate cancer (PCa) remains challenging, and while melatonin (MEL) has demonstrated therapeutic potential, its precise mechanisms require further elucidation. Through integrated in vitro, in vivo, and bioinformatics analyses, this study demonstrated that MEL functioned as a novel ferroptosis inducer in PCa by disrupting androgen receptor (AR) liquid\u2010liquid phase separation (LLPS). We found that MEL effectively inhibited PCa proliferation, migration, and invasion in vitro while suppressing tumor growth safely in mice models. Mechanistically, MEL impaired AR LLPS dynamics, reducing AR\u2010driven transcription of minichromosome maintenance protein 5 (MCM5). MCM5 was a clinically relevant biomarker associated with aggressive PCa and poor survival. Crucially, downregulated MCM5 attenuated its physical interaction with NRF2, leading to uncontrolled activation of the NRF2\/HMOX1 pathway, GPX4 suppression, and accumulation of ferroptosis hallmarks. These findings defined an AR\/MCM5\/NRF2 axis regulating ferroptosis susceptibility, establishing MEL as the first\u2010reported ferroptosis inducer that expands the mechanistic foundation and therapeutic potential of MEL\u2010based PCa treatment strategies.<\/jats:p>","DOI":"10.1111\/jpi.70094","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:21:14Z","timestamp":1761762074000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["\u200cLiquid\u2013Liquid Phase Separation of AR Orchestrated by Melatonin Sensitizes Prostate Cancer to Ferroptosis Via MCM5\/NRF2 Axis Collapse"],"prefix":"10.1111","volume":"77","author":[{"given":"Xianyanling","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Urology, Institute of Urology, West China Hospital Sichuan University Chengdu Sichuan 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