A Review on Ferroptosis an Emerging Form of Regulated Cell Death and Its Pharmacological Relevance

Iron is an essential trace element involved in oxygen transport, energy metabolism, DNA synthesis, and enzymatic functions. However, excess intracellular ferrous iron (Fe²⁺) can generate reactive oxygen species (ROS), leading to oxidative damage of cellular components. Ferroptosis is a unique iron-dependent form of regulated cell death characterized by excessive lipid peroxidation and disruption of cellular antioxidant defenses. Unlike apoptosis, it occurs without caspase activation or DNA fragmentation and is associated with iron overload, mitochondrial dysfunction, and impairment of the cysteine–glutathione–GPX4 pathway. Cells counteract ferroptosis through protective systems such as GPX4, FSP1–CoQ10, GCH1–BH4, and DHODH pathways.Due to its critical role in cancer progression and other diseases, ferroptosis has emerged as an important therapeutic target. Current research focuses on selectively inducing ferroptosis in cancer cells while minimizing damage to normal tissues by targeting key regulators such as GPX4, SLC7A11, and iron metabolism.

Ferroptosis; Iron metabolism; Reactive oxygen species (ROS); Lipid peroxidation; GPX4; Cancer therapy

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