Mollugin induced oxidative DNA damage via up-regulating ROS that caused cell cycle arrest in hepatoma cells

Area of Science:

• Pharmacology
• Molecular Biology
• Oncology

Background:

• Mollugin exhibits anti-tumor properties, but its precise mechanism against hepatocellular carcinoma (HCC) requires further elucidation.
• Hepatocellular carcinoma remains a significant global health challenge, necessitating novel therapeutic agents.

Purpose of the Study:

• To investigate the anti-tumor mechanism of mollugin against HepG2 cells and H22-tumor-bearing mice.
• To explore mollugin's effects on cell cycle progression, DNA damage, and reactive oxygen species (ROS) levels.

Main Methods:

• In vitro studies using HepG2 cells to assess growth inhibition, cell cycle arrest, ROS production, and DNA damage (Comet assay, p-H2AX expression).
• In vivo studies on H22-tumor-bearing mice to evaluate tumor growth inhibition and molecular changes.
• Assessment of key proteins including cyclin A2 and CDK2, and the role of glutathione (GSH) as an antioxidant.

Main Results:

• Mollugin demonstrated significant, dose-dependent inhibition of HepG2 cell growth and suppressed tumor growth in mice.
• Mollugin induced S-phase arrest, DNA damage, and elevated ROS levels in HepG2 cells, effects reversed by GSH.
• In vivo, mollugin decreased tumor cell density and increased ROS in tumor tissue, with consistent molecular changes observed.

Conclusions:

• Mollugin exhibits potent anti-hepatocellular carcinoma activity both in vitro and in vivo.
• The anti-tumor effects of mollugin are mediated by DNA damage and cell cycle arrest, driven by excessive ROS production.
• Mollugin represents a promising candidate for HCC therapy, warranting further investigation.