Work

CHPF2 as a novel biomarker and ponicidin as a potential therapeutic agent in hepatocellular carcinoma

Year: 2025

Type: article

Abstract: Hepatocellular carcinoma (HCC) was associated with high morbidity and mortality, representing a significant health challenge. Chondroitin sulfate (CS), a glycosaminoglycan composed of glucuronic acid and N-acetylgalactosamine, is implicated in HCC progression through its role in cancer cell migration and proliferation as well as interactions with cell surface receptors integrin β-1 and CD44. Chondroitin polymerization factor 2 (CHPF2), the key to CS synthesis, has an undefined role in HCC. Our study aims to demonstrate that decreasing CHPF2 enzyme activity can inhibit the migration and proliferation of HCC cells. Bioinformatics analysis and in vitro experiments on clinical HCC samples confirmed the knockdown of CHPF2 inhibited HCC cell proliferation and migration. We further explored Rabdosia rubescens , a plant used in cancer therapy, for its potential to modulate CHPF2. Structural biology and ligand fishing identified ponicidin, a compound that significantly suppresses HCC cell growth and migration in both in vitro and in vivo models. These findings propose CHPF2 as a novel biomarker and ponicidin as a potential therapeutic agent for HCC management. • Natural medicine Rabdosia rubescens targets CHPF2 to treat HCC. • The direct binding of Ponicidin to CHPF2 was first identified. • Ponicidin inhibits CHPF2 activity,reduce CS production and inhibit HCC cell growth. • Introduce a promising biomarker and drug candidate for clinical HCC treatment.

Source: Pharmacological Research

DOI: 10.1016/j.phrs.2025.107698