GPX4: The core downstream antioxidant of system X c − /GSH/GPX4 axis. As the cornerstone of antioxidant defense, GPX4, a phospholipid peroxidation inhibitor, is the only glutathione peroxidase used for intracellular lipid peroxide reduction (Ursini et al., 1982).

Feb 20, 2021 · Erastin depletes levels of the antioxidant selenoproteins GPX4 and GPX1 in breast cancer cells by inhibiting xCT-dependent extracellular reduction which is required for selenium uptake and selenocysteine biosynthesis.

Aug 29, 2022 · This review aims to present the current understanding of the mechanism of ferroptosis based on the System X c-/GSH/GPX4 axis in the treatment of drug-resistant solid tumors.

Feb 20, 2021 · These findings support the notion that xCT drives the expression of GPX4 , and that the elevated expression of both SLC7A11 and SLC3A2 is a determinant for increased xCT function as indicated by GPX4 expression—And is associated with …

Feb 27, 2024 · xCT/GPX4 axis is involved in the tumor resistance against radiation through the inhibition of ferroptosis in OSCC. Furthermore, radiotherapy combined with ferroptosis induction by targeting the xCT/GPX4 axis may improve patient prognosis in advanced OSCC.

The xCT-GSH-GPX4 axis is the ideal downstream component of ferroptosis that exerts a powerful protective mechanism. Notably, classical xCT inhibitors were capable of leading to the catastrophic accumulation of ROS and exerting synergistic cell death, while xCT overexpression restored these phenomena.

Feb 18, 2025 · Glutathione peroxidase 4 (GPX4) utilizes reduced glutathione (GSH) as a cofactor to detoxify lipid peroxidation and suppress ferroptosis in a GPX4-dependent manner. 12,13 Most cancer cells obtain cysteine mainly through the cystine/glutamate antiporter SLC7A11 (xCT).

Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis, a form of regulated cell death induced by excessive lipid peroxidation.

Jan 1, 2025 · Gastrodin activates the xCT/GPX4 pathway to promote GSH production and reduce lipid peroxides, while inhibiting the ACSL4/LPCAT3 pathway to prevent ferroptosis. These results suggest gastrodin's potential for neuroprotection and stroke recovery by targeting multiple pathways, making it a promising therapeutic option.

The expression levels of xCT ( p < 0.05) and GPX4 ( p < 0.001) were reduced after treatment with erastin and blister fluids, while this phenomenon was reversed by pretreatment with Ferrostatin-1 (Fer-1).