Ursolic acid inhibits the proliferation and migration of breast cancer cells by suppressing the hippo/ YAP signaling pathway

BACKGROUND: Breast cancer (BC) is one of the most frequent malignant tumors, with high morbidity and fatality rates. Abnormalities in the Hippo pathway or YAP overexpression alter the cell proliferation-apoptosis equilibrium, which promotes cancer progression. Ursolic acid (UA), a naturally occurring triterpenoid carboxylic acid, exhibits preventive and anticancer properties. This study aimed to evaluate the effects of UA on breast cancer via the Hippo-YAP pathway. RESULTS: The findings revealed that UA hindered YAP nuclear translocation and increased its phosphorylation, preventing YAP from entering the nucleus from the cytoplasm and thus failing to motivate transcriptional expression of the downstream proliferation-related target genes, including CYR61 (i.e. cysteine-rich 61) and CTGF (i.e. connective tissue growth factor). Moreover, YAP overexpression reversed the inhibitory impact of UA on breast cancer cell proliferation and migration, whereas siYAP increased the inhibitory effects of UA on breast cancer cell proliferation and migration. Additionally, UA inhibited tumor growth in mice xenografted with MCF-7 cells. CONCLUSION: UA reduces breast cancer growth via the Hippo-YAP pathway, providing a theoretical foundation for its anticancer activity and suggesting that UA may serve as a promising candidate for breast cancer therapy.