Artesunate induces ferroptosis of human osteosarcoma cells through p53/SLC7A11/GPX4 axis
10.3969/j.issn.1000-4718.2024.09.005
- VernacularTitle:青蒿琥酯通过p53/SLC7A11/GPX4轴诱导人骨肉瘤细胞铁死亡
- Author:
Ming LI
1
;
Jiangmei JIANG
;
Lijun YAN
;
Qing ZHU
;
Taiding WU
;
Longju CHEN
Author Information
1. 风湿性疾病发生与干预湖北省重点实验室,湖北民族大学医学部,湖北 恩施 445000
- Keywords:
osteosarcoma;
ferroptosis;
p53/SLC7A11/GPX4 signaling pathway;
artesunate
- From:
Chinese Journal of Pathophysiology
2024;40(9):1606-1611
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To explore the promotion of ferroptosis by artesunate(Art)and its underlying mechanism in osteosarcoma.METHODS:Human osteosarcoma U-2 OS cells were divided into 4 groups:control,ferrostatin-1(Fer-1),Art,and Art+Fer-1 groups.Cell viability was measured by CCK-8 assay,while reactive oxygen species(ROS),Fe2+,and glutathione(GSH)levels were measured using biochemical assays.Mitochondrial morphology was evaluated by trans-mission electron microscopy.The mRNA and protein levels of p53,solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)were determined by RT-qPCR and Western blot,respectively.RESULTS:It was found that Art significantly reduced the growth of U-2 osteosarcoma cells,as well as inducing ferroptosis by promoting the accu-mulation of Fe2+and ROS and reducing GSH levels,while the ferroptosis inhibitor ferrostatin-1 inhibited ferroptosis.It was also observed that Art affected mitochondrial morphology,resulting in smaller mitochondria,higher mitochondrial mem-brane density,and reduced numbers of cristae.Treatment with Art also downregulated both the mRNA and protein expres-sion of the ferroptosis-associated genes SLC7A11 and GPX4,while upregulating expression of p53,an upstream regulator of ferroptosis,thus inducing ferroptosis.CONCLUSION:Artesunate induces ferroptosis in osteosarcoma cells through the p53/SLC7A11/GPX4 signaling pathway.
