Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments.
Int J Mol Sci
; 25(15)2024 Jul 29.
Article
en En
| MEDLINE
| ID: mdl-39125853
ABSTRACT
In the development and progression of cervical cancer, oxidative stress plays an important role within the cells. Among them, Solute Carrier Family 7 Member 11 (SLC7A11/xCT) is crucial for maintaining the synthesis of glutathione and the antioxidant system in cervical cancer cells. In various tumor cells, studies have shown that SLC7A11 inhibits ferroptosis, a form of cell death, by mediating cystine uptake and maintaining glutathione synthesis. Additionally, SLC7A11 is also involved in promoting tumor metastasis and immune evasion. Therefore, inhibiting the SLC7A11/xCT axis has become a potential therapeutic strategy for cervical cancer. In this study, through structure-based high-throughput virtual screening, a compound targeting the SLC7A11/xCT axis named compound 1 (PubChem CID 3492258) was discovered. In vitro experiments using HeLa cervical cancer cells as the experimental cell model showed that compound 1 could reduce intracellular glutathione levels, increase glutamate and reactive oxygen species (ROS) levels, disrupt the oxidative balance within HeLa cells, and induce cell death. Furthermore, molecular dynamics simulation results showed that compound 1 has a stronger binding affinity with SLC7A11 compared to the positive control erastin. Overall, all the results mentioned above indicate the potential of compound 1 in targeting the SLC7A11/xCT axis and treating cervical cancer both in vitro and in silico.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias del Cuello Uterino
/
Especies Reactivas de Oxígeno
/
Sistema de Transporte de Aminoácidos y/
/
Simulación de Dinámica Molecular
/
Glutatión
Límite:
Female
/
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2024
Tipo del documento:
Article
País de afiliación:
China