Life Sci. 2025 Dec 26;387:124175. doi: 10.1016/j.lfs.2025.124175. Online ahead of print.
ABSTRACT
Low adiponectin levels in obese men are associated with an incidence of aggressive prostate cancer (PCa). Despite significant advances in PCa treatment, some cases become resistant, making the development of new therapies crucial. An alternative treatment is the use of agonists, such as AdipoRon. Here, we elucidate the antitumor effects of AdipoRon on PCa models and demonstrate reduced cell proliferation, migration, and invasion in vitro. AdipoRon impaired mitochondrial respiration of androgen-dependent and castration-resistant cells. We show that this agonist reduces AR and PSA expression in androgen-dependent prostate cells. Adiponectin receptors (AdipoR1 and AdipoR2) were upregulated in PC3 and DU-145 cells. We hypothesize that the alteration of PPAR alpha could explain the effects of AdipoRon. Additionally, the antigrowth effects of AdipoRon were observed in the patient-derived organoids PM154 and MSK-PCa16. Our findings reveal that AdipoRon has strong in vitro antitumor effects on PCa, supporting its potential as a promising therapeutic candidate. Future studies should focus on in vivo models to validate these effects and explore the underlying mechanisms, which may open new therapies for PCa. STATEMENT OF IMPLICATION: AdipoRon decreases prostate cancer cell growth.
PMID:41456807 | DOI:10.1016/j.lfs.2025.124175