Mechanism of esculetin promoting ferroptosis of mouse breast cancer 4T1 cells based on p53/SLC7A11/GPX4 axis
10.3969/j.issn.1000-4718.2024.02.011
- VernacularTitle:基于p53/SLC7A11/GPX4信号轴探讨七叶内酯诱导小鼠乳腺癌4T1细胞铁死亡的作用机制
- Author:
Dan HE
1
,
2
;
Linpei LI
;
Xiaoning TAN
;
Wenhui GAO
;
Xuefei TIAN
;
Puhua ZENG
Author Information
1. 湖南省中医药研究院,湖南 长沙 410006
2. 湖南中医药大学中西医结合学院,湖南 长沙 410208
- Keywords:
breast cancer;
esculetin;
ferroptosis;
p53/SLC7A11/GPX4 signaling pathway
- From:
Chinese Journal of Pathophysiology
2024;40(2):282-290
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the mechanism through which esculetin induces ferroptosis of mouse breast cancer 4T1 cells.METHODS:Molecular docking of esculetin with p53,solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)proteins was performed,and Kaplan-Meier curves and time-dependent receiver oper-ating characteristic curves were drawn.The 4T1 cells were divided into 6 groups,namely the control(CON),1/2 IC50,IC50,2 IC50,erastin,and capecitabine groups.The appropriate drug concentration for treating 4T1 cells was screened by CCK-8 assay.The invasion and migration abilities of 4T1 cells following esculetin treatment at the selected drug concentra-tion were analyzed by scratch test and Transwell assay.Mitochondrial morphological change were examined by electron mi-croscopy.The levels of ferroptotic cell death were then quantified by Fe2+,reactive oxygen species(ROS),malondialde-hyde(MDA),glutathione(GSH),and GPX4 assays.Western blot was performed to evaluate the protein levels of p53,SLC7A11,GPX4 and acyl-CoA synthetase long-chain family member 4(ACSL4).RESULTS:Compared with CON group,the esculetin 1/2 IC50,IC50 and 2 IC50 groups showed smaller size,increased membrane density,and decreased ridge of mitochodria,as well as decreased levels of GSH and GPX4,reduced cell invasion and migration abilities,and de-creased levels of SLC7A11 and GPX4 proteins(P＜0.05).Furthermore,these groups exhibited increased levels of Fe2+,ROS,and MDA,as well as elevated p53 and ACSL4 protein abundance(P＜0.05).CONCLUSION:Esculetin pro-motes ferroptosis of 4T1 cells through a mechanism involving the p53/SLC7A11/GPX4 regulatory axis.
