Oxidative Stress and Hepatocellular Carcinoma Mechanisms

Oxidative stress arises when the generation of reactive oxygen species (ROS) outpaces the hepatocyte’s antioxidant defences, triggering lipid peroxidation, DNA damage and protein dysfunction. In chronic liver injury—from viral hepatitis, alcohol misuse or metabolic disorders—persistent ROS accumulation promotes mutations in oncogenes and tumour suppressors, activates pro-inflammatory transcription factors such as nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3), and impairs redox-sensitive signalling pathways. Mitochondrial dysfunction and endoplasmic reticulum stress further amplify ROS production, creating a self-sustaining cycle that drives hepatocellular carcinoma (HCC) initiation and progression. Key events include compensatory proliferation after cell death, epithelial-mesenchymal transition, angiogenesis and the emergence of drug-resistant cancer stem cell populations. Conversely, adaptive activation of antioxidant programmes—chiefly via nuclear factor erythroid 2-related factor 2 (Nrf2)—can confer survival advantages on transformed cells, undermining chemotherapy and targeted agents. Understanding these intersecting redox and signalling networks has global significance for early detection, prognostic stratification and the design of therapies that restore redox balance while selectively eliminating malignant hepatocytes.

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Oxidative Stress and Hepatocellular Carcinoma Mechanisms publication trend

The graph below shows the total number of articles in oxidative stress and hepatocellular carcinoma mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): chemically reactive oxygen derivatives that can damage DNA, lipids and proteins.

Oxidative stress: state in which ROS production exceeds cellular antioxidant capacity.

Nuclear factor erythroid 2–related factor 2 (Nrf2): transcription factor orchestrating the expression of antioxidant and cytoprotective genes.

Apoptosis: programmed cell death characterised by caspase activation and controlled dismantling of cellular components.

Necroptosis: regulated form of necrotic cell death mediated by receptor-interacting protein kinases.

References

1. Oxidative Stress and Liver Cancer: Etiology and Therapeutic Targets. Oxidative Medicine and Cellular Longevity (2016).
2. Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights. Antioxidants (2022).
3. Effects of Sorafenib and Quercetin Alone or in Combination in Treating Hepatocellular Carcinoma: In Vitro and In Vivo Approaches. Molecules (2022).
4. The Carcinogenic Agent Diethylnitrosamine Induces Early Oxidative Stress, Inflammation and Proliferation in Rat Liver, Stomach and Colon: Protective Effect of Ginger Extract. Asian Pacific Journal of Cancer Prevention (2019).