Cardionogen-1, a novel small molecule, induces cytotoxicity by inhibiting Wnt/β-catenin signalling pathway in Huh-7...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Hepatocellular carcinoma (HCC) remains a significant global health challenge with limited effective targeted therapies.
• The Wnt/β-catenin signaling pathway is frequently dysregulated in liver cancer, making it a potential therapeutic target.

Purpose of the Study:

• To investigate the anticancer properties of cardionogen-1 (CDNG-1), a novel small molecule inhibitor of the Wnt/β-catenin pathway.
• To evaluate the effects of CDNG-1 on human hepatoma Huh-7 cell viability, proliferation, migration, apoptosis, and cell cycle progression.

Main Methods:

• Huh-7 cells were treated with varying concentrations of CDNG-1 (5, 10, 20 µM/ml) for 24 hours.
• Assays included cytotoxicity, reactive oxygen species (ROS) analysis, apoptosis evaluation, scratch assay, flow cytometry, PCR, and Western blotting.
• Key protein and gene expression related to apoptosis, cell cycle, and Wnt/β-catenin signaling were analyzed.

Main Results:

• CDNG-1 significantly inhibited Huh-7 cell viability, proliferation, and migration in a dose-dependent manner.
• Treatment with CDNG-1 induced ROS-mediated early apoptosis and intrinsic apoptosis, evidenced by altered expression of apoptosis-related proteins (Bax, Bcl-2, p53, p21, cytochrome c).
• CDNG-1 disrupted the cell cycle, causing accumulation in G0/G1, S, and G2/M phases, and downregulated cell cycle regulators (cyclin D, CDK-4). The Wnt/β-catenin pathway was inhibited, with decreased Wnt3, LRP6, and β-catenin expression.

Conclusions:

• CDNG-1 exhibits potent anti-proliferative, anti-migratory, and pro-apoptotic effects in liver cancer cells.
• The compound acts, in part, by inhibiting the Wnt/β-catenin signaling pathway and inducing oxidative stress and apoptosis.
• CDNG-1 represents a promising therapeutic candidate for targeted liver cancer treatment.