Open Access

REVIEW

Ferroptosis Mediates Zinc Toxicity: Implications for Cancer Therapy

Anton Tkachenko^*

BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, Vestec, 252 50, Czech Republic

* Corresponding Author: Anton Tkachenko. Email:

BIOCELL 2025, 49(5), 721-741. https://doi.org/10.32604/biocell.2025.063301

Received 10 January 2025; Accepted 03 March 2025; Issue published 27 May 2025

Abstract

Ferroptosis is an iron-driven, phospholipid hydroperoxide-mediated cell death, which has recently emerged as an attractive tool in cancer research due to its ability to govern the anti-tumor immune response. A growing research interest in ferroptosis biology has revealed the contribution of this regulated cell death to multiple diseases. In addition to iron, ferroptosis has been reported to be triggered by multiple heavy metals, which sheds light on the novel aspects of heavy metals-induced cytotoxicity. In this review, the ability of zinc, an essential biogenic element with a wide array of biological functions, to modulate ferroptosis in normal and malignant cells has been summarized. Accumulating evidence suggests that zinc-induced biological effects can be mediated by ferroptosis induction or attenuation. In addition, the anti-cancer effects of zinc can be at least partly attributed to ferroptosis induction. The signaling pathways governing zinc-regulated ferroptosis are highlighted. It has been underscored that zinc-mediated modulation of ferroptosis is dependent on alterations of redox homeostasis, antioxidant defense (in particular, the SLC7A11/GSH/GPX4 axis), and iron metabolism. Additionally, data on ferroptosis induction by zinc oxide nanoparticles are summarized to emphasize the potential of these nanomaterials as a promising therapeutic choice in anti-cancer treatment.

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Keywords

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