Monacolin X Modulates Cellular Antioxidant Defense by Disrupting Reactive oxygen species in HepG2 Liver Cancer Cells

Cancer Biology lab, Centre for Molecular and Nanomedical Sciences, Sathyabama Institute of Science and Technology, Chennai - 600119, Tamil Nadu, India

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Published online: 10 March 2026

Abstract

Hepatocellular carcinoma (HCC) is one of the leading aggressive malignancies worldwide, characterized by metabolic reprogramming and redox imbalance that support tumor progression and survival. Monacolin X, a bioactive secondary metabolite, has recently gained attention for its potential anticancer properties; however, its underlying molecular mechanisms remain poorly understood. The present study investigates the effect of Monacolin X on cellular antioxidant defense in HepG2 (liver cancer cells). HepG2 (liver cancer) cells were treated with Monacolin X, and alterations were assessed through key metabolic indicators, along with evaluation of oxidative stress markers and antioxidant enzyme levels. Our findings demonstrate that Monacolin X significantly disrupts energy homeostasis in HepG2 cells. This metabolic disruption was accompanied by increased intracellular reactive oxygen species (ROS) levels and modulation of antioxidant defense systems, including changes in enzymatic antioxidants. The combined effects resulted in increased oxidative stress, contributing to reduced cell viability and enhanced susceptibility to cell death. Overall, this study highlights Monacolin X as a promising metabolic modulator that targets redox balance in liver cancer cells, providing mechanistic insights into its potential therapeutic application against hepatocellular carcinoma.