Cellular metabolism: A key player in cancer ferroptosis

Abstract

Cellular metabolism is the fundamental process by which cells maintain growth and self‐renewal. It produces energy, furnishes raw materials, and intermediates for biomolecule synthesis, and modulates enzyme activity to sustain normal cellular functions. Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis is a recently discovered form of iron‐dependent programmed cell death. The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression. However, the role of cellular metabolism, particularly glucose and amino acid metabolism, in cancer ferroptosis is not well understood. Here, we reviewed glucose, lipid, amino acid, iron and selenium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process. Additionally, we provided a detailed overview of agents used to induce cancer ferroptosis. We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellular redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron‐induced cell death, resulting in enhanced tumor cell killing. The combination of ferroptosis inducers and cellular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.

MDH2 Promotes Hepatocellular Carcinoma Growth through Ferroptosis Evasion via Stabilizing GPX4

“…MDH2 plays a crucial role in catalyzing the dehydrogenation of malate, leading to the production of oxaloacetate and NADH, which subsequently generates NADPH [28]. NADPH serves as an essential cofactor in the reduction process of GPX4, which facilitates the removal of peroxidized lipids from cells [29]. Notably, both MDH2 and GPX4 are localized in mitochondria, which leads us to speculate that there may be a potential relationship between them that could impact ferroptosis in HCC.…”

Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

“… 6 It is triggered by glutathione (GSH) depletion, decreased activity of glutathione peroxidase 4 (GPX4), failure of lipid oxides to be metabolized by GPX4, and Fe 2+ -mediated oxidation of lipids leading to the generation of reactive oxygen species (ROS) that promote ferroptosis. 7 Ferroptosis provides a new way of thinking about cancer treatment. Ferroptosis induction therapy has several natural advantages for cancer treatment.…”