Ebselen Suppresses Breast Cancer Tumorigenesis by Inhibiting YTHDF1-Mediated c-Fos Expression

YTHDF1, an N6-methyladenosine (m⁶A)-binding protein, plays a key role in breast cancer progression, yet its therapeutic targeting remains underexplored. In this study, we investigated the anticancer effects of the novel YTHDF1 inhibitor ebselen in breast cancer cells. Ebselen treatment reduced cell viability in a dose-dependent manner and induced apoptosis, as demonstrated by Annexin V staining, Sub-G1 accumulation, and DNA fragmentation. Consistently, ebselen increased reactive oxygen species (ROS) production and impaired autophagy induction. Mechanistically, ebselen impaired YTHDF1-mediated stabilization and translation of FOS mRNA, leading to decreased c-Fos expression. In addition, ebselen suppressed anchorage-independent growth in vitro and significantly reduced tumor growth in an orthotopic mouse model. These findings highlight YTHDF1 as a promising therapeutic target and support ebselen as a potential small-molecule inhibitor for breast cancer treatment.