Fucoidan Provokes Ferroptosis via Inhibition of the PI3K/Akt Signaling Pathway in Human Osteosarcoma 143B Cells
10.13865/j.cnki.cjbmb.2025.07.1162
- VernacularTitle:岩藻多糖通过抑制PI3K/Akt通路诱导人骨肉瘤143B细胞铁死亡
- Author:
Qiao LIN
1
;
Qi-Qi WANG
1
;
Xin-Yi BAO
1
;
Yu-Ting WANG
1
;
Lu-Bing ZHANG
1
;
Yi-Ning FAN
1
;
Jian FANG
1
;
Yun ZHANG
1
Author Information
1. 绍兴文理学院医学院生理学教研室,浙江 绍兴 312000
- Publication Type:Journal Article
- Keywords:
fucoidan(FUC);
143B cells;
ferroptosis;
PI3K/Akt signaling pathway
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(9):1298-1309
- CountryChina
- Language:Chinese
-
Abstract:
Fucoidan(FUC)is a natural seaweed-derived drug.Previously,our experiments have shown that FUC can significantly inhibit the cell viability of human osteosarcoma 143B cells and induce cell death,but the mechanism remains unclear.Ferroptosis,a novel form of cell death,has emerged as an important target for tumor therapy.This study aims to investigate whether FUC induces ferroptosis of 143B cells and elucidate its underlying molecular mechanisms.CCK-8 and LDH assays result showed that FUC(10,100,400 μg/mL)significantly reduced cell viability of 143B cells and induced cell death.Calce-in-AM staining,FeRhoNox-1 staining,and C11 BODIPY 581/591 staining indicated that FUC obviously increased the levels of labile iron pool(LIP),Fe2+,and lipid reactive oxygen species(Lip ROS)in 143B cells.Chemical colorimetric analysis revealed that FUC markedly decreased intracellular Glutathi-one(GSH)contents.Real-time quantitative PCR showed that FUC dramatically reduced the mRNA lev-els of ferroptosis-related factors solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while increasing the mRNA levels of prostaglandin endoperoxide synthase 2(PTGS2)and acyl-CoA synthetase long-chain family member 4(ACSL4).Western blotting analysis demonstrated that FUC significantly reduced the protein levels of SLC7A11 and GPX4,and the ratios of p-PI3K/PI3K,p-AktSer473/Akt,and p-AktThr308/Akt,but increased the protein level of ACSL4.Immunofluorescence staining showed that FUC obviously inhibited the nuclear translocation of p-AktSer473.The ferroptosis in-hibitor ferrostatin-1(Fer-1)and iron chelator deferoxamine(DFO)remarkably suppressed cell death in-duced by FUC in 143B cells.Additionally,the PI3K/Akt pathway activator 740Y-P significantly inhibi-ted FUC-induced iron overload and lipid peroxidation in 143B cells,and restored the protein levels of SLC7A11 and GPX4.In conclusion,FUC can induce ferroptosis of 143B cells by inhibiting the PI3K/Akt signaling pathway,which may be a potential target for the prevention and treatment of osteosarcoma.
