Therapeutic Suppression of Triple-Negative Breast Cancer via Pachymic Acid-Induced KIF18B Inhibition and Ferroptosis Activation.

Triple-negative breast cancer (TNBC) is a particularly aggressive malignant tumor. Pachymic acid (PA), a bioactive triterpenoid, has demonstrated multi-target therapeutic effects in TNBC. However, the detailed molecular networks responsible for its anti-TNBC effects have not yet been fully elucidated. The therapeutic potential of PA was evaluated by measuring cell viability, proliferation, invasion, and migration. The impact on ferroptosis was assessed by detecting ROS, MDA, GSH, and Fe2⁺ levels. Animal xenograft experiments were used to analyze the role in vivo. Expression analysis was performed using immunoblot, quantitative PCR, and immunohistochemical assays. PA exhibited antiproliferative, anti-migratory, and anti-invasive effects on BT-549 and MDA-MB-231 cells in vitro. PA induced oxidative stress and triggered ferroptosis in BT-549 and MDA-MB-231 cells. Kinesin family member 18B (KIF18B) was overexpressed in TNBC and was reduced by PA treatment. KIF18B restoration counteracted PA-mediated antiproliferative, anti-migratory, anti-invasive, and pro-ferroptosis effects on BT-549 and MDA-MB-231 cells. Furthermore, restored expression of KIF18B attenuated the efficacy of PA in reducing xenograft growth in vivo. Our study demonstrates that PA suppresses TNBC progression by inducing ferroptosis and inhibiting malignant phenotypes through KIF18B downregulation, offering experimental evidence supporting the clinical potential of PA as a novel therapeutic agent for TNBC treatment.