Celastrol sensitizes bicalutamide to enhance immunogenic Cell death in the treatment of castration-resistant prostate

BackgroundProstate cancer is the most commonly diagnosed non-cutaneous malignancy in men and is the second-leading cause of cancer-related death. Castration-resistant pr ostate cancer (CRPC) persists despite low testosterone levels. MethodsIn this study, we investigated the combined effect of Celastrol and bicaluta mide on prostate cancer cells. We evaluated cytotoxicity, apoptosis, oxidative stress, ferro ptosis and the activation of the immune system in vivo and in vitro. ResultsOur findings revealed that the co-administration of Celastrol with bicalutamide enhanced cytotoxicity against prostate cancer cells, promoted cell apoptosis, induced oxi dative stress and ferroptosis. Importantly, it assisted bicalutamide in activating the immune system, triggering immunogenic cell death (ICD), and thereby enhancing immune thera py. This synergy resulted in a stronger anti-CRPC effect, improving the overall therapeutic efficacy. ConclusionOur study demonstrates the potential of the Celastrol and bicalutamide combination in treating castration-resistant prostate cancer. Further studies are warranted to explore the clinical application of this approach and its potential in improving patient outcomes. Funding informationThe author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by Beijing Municipal Natural Science F oundation (grant no. BFHHQS20240003).