Therapeutic Potential of Flavonoids in Modulating Mitochondrial Activity in Liver Cancer: Insights from HepG2 Cell Studies

Abstract

Background: Cancer, a leading cause of mortality globally, affects various organs, including the liver, with liver cancer contributing to approximately 830,000 deaths in 2020. In Malaysia, liver cancer is increasingly prevalent. The HepG2 cell line, derived from human hepatoma, is widely used for studying liver cancer and drug-induced liver injuries. Flavonoids, a group of polyphenolic compounds found in plants, have gained attention for their diverse pharmacological activities, including their potential to mitigate carcinogenesis and tumorigenesis in liver cancers. Methods: This review synthesizes findings from studies investigating the impact of flavonoids on liver cancer, focusing on the HepG2 cell line. We explore flavonoid subtypes and their therapeutic roles, including their antioxidant, anti-inflammatory, anti-angiogenic, and cytotoxic properties. Research on mitochondrial function in cancer cells and how flavonoids influence mitochondrial activity in the HepG2 cell line is also assessed. Results: Flavonoids demonstrated significant antioxidant properties by modulating reactive oxygen species (ROS) levels and maintaining mitochondrial homeostasis in HepG2 cells. Key flavonoids, including quercetin, naringenin, and kaempferol, exhibited strong anti-inflammatory and anti-angiogenic effects. Furthermore, cytotoxic flavonoids induced apoptosis in HepG2 cells through mitochondrial disruption and ROS generation, with certain compounds showing selective toxicity to cancer cells. Conclusion: Flavonoids exhibit promising therapeutic potential in liver cancer by targeting oxidative stress, inflammation, and angiogenesis while promoting apoptosis in HepG2 cells. Their ability to modulate mitochondrial function positions them as potent agents for further investigation in liver cancer therapy.