Inhibition of Thioredoxin-Reductase by Auranofin as a Pro-Oxidant Anticancer Strategy for Glioblastoma: In Vitro and In Vivo Studies

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2084 - 2084

Published: Feb. 27, 2025

Reactive oxygen species (ROS) play a key role in cancer progression and antitumor therapy. Glioblastoma is highly heterogeneous tumor with different cell populations exhibiting various redox statuses. Elevated ROS levels cells promote growth simultaneously make them more sensitive to anticancer drugs, but further elevation leads death apoptosis. Meanwhile, subsets of cells, such glioblastoma stem (GSC) or the microenvironment (TME), demonstrate adaptive mechanisms excessive production by developing effective antioxidant systems as glutathione- thioredoxin-dependent. GSCs higher chemoresistance lower than other glioma while TME create pro-oxidative environment have immunosuppressive effects. Both subpopulations become an attractive target for therapies. Increased expression thioredoxin reductase (TrxR) often associated poor patient survival. Various TrxR inhibitors been investigated potential therapies, including nitrosoureas, flavonoids metallic complexes. Gold derivatives are irreversible TrxR. Among them, auranofin (AF), selective inhibitor, has proven its effectiveness drug treatment rheumatoid arthritis efficacy agent demonstrated preclinical studies vitro vivo. However, clinical application AF could be challenging due low solubility insufficient delivery glioblastoma. Different strategies hydrophobic drugs used increase concentration brain. Combining therapeutic approaches that affect status new strategy treating brain diseases.

Language: Английский

Ferroptosis in hepatocellular carcinoma: Mechanisms and therapeutic implications

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 182, P. 117769 - 117769

Published: Dec. 16, 2024

Language: Английский

Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1201 - 1201

Published: Oct. 3, 2024

Glioblastoma (GBM) is an incurable primary brain cancer characterized by increased reactive oxygen species (ROS) production. The redox-sensitive tumor suppressor gene

Language: Английский