ABSTRACT
To develop an inhibitor targeting the Wnt/ß-catenin signaling pathway, flavonoid monomer that can interact with ß-catenin was isolated from Paulownia flowers. Luteolin may form stable hydrogen bonds with ß-catenin by molecular docking. Fluorescence quenching analysis determined the physical interaction between luteolin and ß-catenin. The binding of luteolin to ß-catenin caused a loss of α-helical structure and induced a conformational change through circular dichroism spectroscopy. Luteolin inhibits the activity of the Wnt signaling, causing cholangiocarcinoma (CCA) cell cycle arrest in the G2/M phase, leading to cell apoptosis and inhibition of cell migration. In addition, transcriptome and proteomics analysis showed that the differentially expressed proteins were significantly enriched in the Wnt/ß-catenin pathway. ß-catenin protein in the nucleus was significantly decreased, while C-Myc and cyclin D1 in the CCA cells were significantly decreased after luteolin treatment. Additionally, activation of the Wnt/ß-catenin signaling reversed the inhibitory effect of luteolin on the migration of CCA cells. Therefore, luteolin can directly interact with ß-catenin and act as an inhibitor of ß-catenin, inhibiting proliferation and reducing the migration ability of CCA cells by inhibiting the Wnt/ß-catenin pathway. This study provides a scientific basis for the development of Wnt/ß-catenin pathway inhibitors and the prevention and treatment of CCA.