Mechanism of benzophenone-3 in promoting proliferation and migration of prostate cancer cells via the acyl-CoA dehydrogenase 9 axis

Prostate cancer (PCa) remains one of the most common malignancies in men, with rising global incidence and mortality rates. Recently, the impact of environmental pollutants on PCa initiation and progression has garnered significant attention. Benzophenone-3 (BP3), a ubiquitous ultraviolet filter in personal care products, possesses potential endocrine-disrupting and pro-carcinogenic properties; however, its specific role in PCa remains poorly defined. In this study, we demonstrated that BP3 significantly promoted PCa cell proliferation and migration. A BP3-derived nomogram was developed, which not only predicted PCa prognosis but also revealed an associated immunosuppressive microenvironment characterized by increased Treg and M2 macrophage infiltration alongside decreased CD8⁺ T cell populations. Mechanistic investigations identified acyl-CoA dehydrogenase 9 (ACAD9) as a pivotal mediator of these effects, as ACAD9 knockdown effectively reversed BP3-induced oncogenic phenotypes. Functional assays further elucidated that BP3 accelerates the fatty acid oxidation (FAO) rate while suppressing reactive oxygen species (ROS) production, a metabolic shift abrogated by ACAD9 silencing. Finally, in vivo xenograft models validated that BP3 monotherapy markedly promotes PCa progression, whereas ACAD9 deficiency neutralizes this effect. In summary, our findings characterized BP3 as an environmental pro-carcinogen that drives PCa malignancy via the BP3/ACAD9 axis, offering new insights into environmental risk factors and potential therapeutic targets for PCa. • BP3 promotes prostate cancer cell proliferation, migration, and EMT in a dose-dependent manner. • ACAD9 acts as a metabolic mediator of BP3-induced oncogenic effects in prostate cancer cells. • Targeting the BP3/ACAD9 axis provides a novel therapeutic strategy for prostate cancer intervention.