Oleanolic acid derivatives inhibit the Wnt/β-catenin signaling pathway by promoting the phosphorylation of β-catenin in human SMMC-7721 cells

Oleanolic acid, isolated from privet, has shown antitumor effects in several cancers. However, the underlying molecular mechanism associated with these effects is largely unknown. In this study, we explored the effect of oleanolic acid derivatives on the Wnt/β-catenin signaling pathway in human hepatocellular carcinoma SMMC-7721 cells. The mRNA and protein levels of related genes were determined by real-time quantitative PCR and Western blot, respectively. Treatment of SMMC-7721 cells with oleanolic acid derivatives led to the downregulation of the mRNA and protein levels of β-catenin, c-myc, and cyclin D1. Treatment with oleanolic acid derivatives decreased the levels of β-catenin in both the cytoplasm and the nucleus. Moreover, oleanolic acid derivatives promoted the phosphorylation of β-catenin (Ser33/37/Thr41) in the cytoplasm. Our results suggest that oleanolic acid derivatives inhibit the Wnt/β-catenin signaling pathway by stimulating the phosphorylation of β-catenin (Ser33/37/Thr41) in human SMMC-7721 cells.