Anti-tumor Activity of the Small Molecule Inhibitor PRI-724 Against β-Catenin-activated Hepatocellular Carcinoma

Background/Aim: CBP is a transcriptional coactivator involved in the Wnt/β-catenin pathway, which plays a role in regulating cell kinetics and differentiation. This study aimed to characterize hepatocellular carcinoma (HCC) with β-catenin activation and assess the direct effects of PRI-724, a selective inhibitor of Wnt/β-catenin/CBP signaling, on HCC.

Materials and Methods: Immunohistochemistry for β-catenin was performed on 199 resected HCC samples. Additionally, HCC cell lines were treated with C-82, the active form of PRI-724, to analyze cell kinetics and related protein expression.

Results: Nuclear β-catenin expression was observed in 18% of HCC cases, and these tumors were larger in size. In HCC cell lines with constitutively active β-catenin, C-82 treatment inhibited cell ICG-001 proliferation. C-82 also increased the proportion of cells in the G0/G1 phase and the sub-G1 phase. Furthermore, C-82 significantly reduced the expression of proliferation markers while upregulating apoptosis-related proteins.

Conclusion: PRI-724 (C-82) shows potential as a novel therapeutic agent for treating β-catenin-activated HCC.