Celastrol induces ferroptosis by suppressing RRM2 in hepatocellular carcinoma.
Heliyon
; 10(13): e33936, 2024 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-39071636
ABSTRACT
Introduction and Objectives:
Ferroptosis is a novel form of cell death driven by iron dependence and lipid peroxidation, presenting a promising potential as an innovative strategy for cancer treatment. Celastrol (Cel) is particularly effective in inducing ferroptosis, but its molecular mechanism remains unclear. The study aims to elucidate the potential mechanism through both in vitro and in vivo experiments. Materials andmethods:
CCK-8 assay, Western blot analysis and measurements of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) were performed to investigate how Cel inhibits the proliferation of hepatocellular carcinoma (HCC) cells via the ferroptosis mechanism. Bioinformatics analysis based on the TCGA-LIHC and FerrDb databases was performed to identify the target gene RRM2, and molecular docking-simulated binding between RRM2 and Cel. The role of RRM2 in the effects of Cel was determined through lentiviral transfection, Transwell assays, and in vivo experiments.Results:
Cel inhibited HCC cell proliferation via the ferroptosis pathway. Inhibition RRM2 significantly reduces mTOR protein phosphorylation, while overexpressing RRM2 can attenuate theeffects of Cel on the proliferation, migration, invasion, and ferroptosis induction of HCC cells. The result of in vivo experiments in nude mice demonstrated that Cel inhibited tumor growth without adversely affecting liver and kidney function indicators. Immunohistochemistry and Western blot analyses revealed that Cel activated the key proteins in the ferroptosis pathway and affected crucial indicators such as malondialdehyde (MDA) and glutathione (GSH).Conclusion:
In this study, we clarifiy the molecular mechanism of Cel, thus broadening its clinical applications for treating various cancer types, including liver cancer.
Texto completo:
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Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Heliyon
Año:
2024
Tipo del documento:
Article
País de afiliación:
China