Oxidative Stress Modulation in Cancer Cells

Cancer cells frequently exhibit elevated levels of reactive oxygen species (ROS) as a consequence of accelerated metabolism, mitochondrial dysfunction and oncogene activation. While moderate increases in ROS can promote proliferation and survival through redox‐sensitive signalling, excessive ROS accumulation damages proteins, lipids and nucleic acids, triggering cell death programmes. To survive, tumour cells invoke adaptive responses that enhance antioxidant defences, including upregulation of glutathione synthesis, activation of redox enzymes and modulation of autophagy. Recent efforts have sought to exploit this fragile balance by tipping cancer cells beyond their oxidative threshold or by simultaneously inhibiting antioxidant systems. Such strategies encompass the use of small molecules that induce ROS generation, compounds that block glutathione recycling, agents that inhibit redox‐sensitive kinases and modulators of autophagy. Emerging evidence demonstrates that selective activation of oxidative stress can impair rRNA transcription, deregulate histone demethylases and engage caspase‐dependent apoptosis. Moreover, combinations of pro‐oxidant drugs with inhibitors of antioxidant enzymes are under investigation for synergistic effects. The global significance of these approaches lies in their potential to overcome resistance to conventional therapies, to target hard‐to‐treat tumours and to achieve selective toxicity. Translational studies are now confronting challenges of drug delivery, tumour heterogeneity and off‐target toxicity, with several candidates advancing to early clinical evaluation.

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Oxidative Stress Modulation in Cancer Cells publication trend

The graph below shows the total number of articles in oxidative stress modulation in cancer cells across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Partially reduced oxygen derivatives (e.g. superoxide, hydrogen peroxide) that function in signalling but cause macromolecular damage when in excess.

Glutathione (GSH): The principal intracellular thiol antioxidant that detoxifies ROS and maintains redox homeostasis.

Autophagy: A lysosome-mediated degradative process that recycles cellular components under stress, which can be cytoprotective or cytotoxic in cancer contexts.

Caspases: A family of cysteine proteases that execute apoptosis through proteolytic cleavage of key substrates.

Lysine demethylase 2A (KDM2A): A Jumonji-C histone demethylase that targets H3K36me2 marks, regulating rRNA gene transcription and cell proliferation.

References

1. Propyl gallate inhibits hepatocellular carcinoma cell growth through the induction of ROS and the activation of autophagy. PLOS ONE (2019).
2. Gallic Acid Derivatives Propyl Gallate and Epigallocatechin Gallate Reduce rRNA Transcription via Induction of KDM2A Activation. Biomolecules (2021).
3. The Anti-Apoptotic Effects of Caspase Inhibitors in Propyl Gallate-Treated Lung Cancer Cells Are Related to Changes in Reactive Oxygen Species and Glutathione Levels. Molecules (2022).