@article{TCR120506,
author = {Li-Ying Sun and Peng Huang and Yan-Hua Su},
title = {Garcinoic acid promotes ferroptosis-associated growth inhibition in esophageal squamous cell carcinoma through an MDM2-associated mechanism},
journal = {Translational Cancer Research},
volume = {15},
number = {7},
year = {2026},
keywords = {},
abstract = {Background: Garcinoic acid (GA), a plant metabolite, has been shown to exhibit anti-inflammatory and antioxidant activities; however, its mechanism of action against esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to investigate the effects of GA on ESCC and to elucidate its underlying molecular mechanisms.Methods: The anti-ESCC effects of GA were evaluated using cell counting kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) staining, acridine orange/ethidium bromide (AO/EB) staining, and Transwell assays. Ferroptosis-associated changes were assessed using C11-BODIPY staining, reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), and glutathione (GSH) assays, transmission electron microscopy, and Western blotting of ferroptosis-associated proteins. Network pharmacology and Mendelian randomization were employed to prioritize candidate mediators linking GA, ESCC, and ferroptosis. Molecular docking and molecular dynamics simulations were performed to predict potential GA-mouse double minute 2 (MDM2) interactions and assess complex stability. Rescue experiments were conducted to evaluate the functional relevance of MDM2.Results: GA inhibited ESCC cell proliferation, induced apoptosis, and reduced cell migration. GA increased levels of MDA and Fe2+, and induced GSH depletion. Pretreatment with Ferrostatin-1 attenuated GA-induced inhibition of cell viability. MDM2 was prioritized as a candidate mediator linking GA, ESCC, and ferroptosis. Molecular docking predicted a favorable binding affinity between GA and MDM2, with a binding energy of −9.1 kcal/mol. Molecular dynamics simulations suggested that the predicted GA-MDM2 complex remained stable under the simulation conditions. Rescue experiments demonstrated that MDM2 may mediate GA-associated ferroptosis and growth inhibition in ESCC cells.Conclusions: These findings suggest that GA induces ferroptosis-associated growth inhibition in ESCC cells, potentially through an MDM2-associated mechanism, and provide a rationale for further investigation of GA-related ferroptosis modulation in ESCC.},
issn = {2219-6803}, url = {https://tcr.amegroups.org/article/view/120506}
}