Effect and molecular mechanism of hesperadin-induced ferroptosis in chronic myeloid leukemia K562 cells
10.3760/cma.j.cn121090-20231218-00323
- VernacularTitle:橙皮苷诱导慢性髓性白血病细胞系K562细胞发生铁死亡的作用及分子机制
- Author:
Junyi WEI
1
;
Long LI
;
Huimin LIU
Author Information
1. 山西医科大学第二医院血液科，太原 030001
- Keywords:
Leukemia, myeloid, chronic;
Hesperadin;
Ferroptosis;
SLC7A11/GPX4 axis
- From:
Chinese Journal of Hematology
2024;45(6):577-585
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect and molecular mechanism of hesperadin in inducing ferroptosis in chronic myeloid leukemia cell line K562 cells.Methods:The effects of hesperadin on the viability, proliferation, and migration of K562 cells were detected though CCK8, EDU-594, and Transwell assays, and the apoptotic rate of K562 cells was detected by flow cytometry. In addition, C11-BODIPY and FerroOrange were utilized to detect intracellular lipid peroxidation and Fe 2+ levels. Meanwhile, the expression levels of ferroptosis-associated protein solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in cells were detected through Western blot. Lipid peroxidation and Fe 2+ levels were also detected after transfection of cells with SLC7A11 overexpression plasmid. Results:Hesperadin decreased cell viability in a dose-dependent manner with IC 50 of 0.544 μmol/L. Hesperadin concentrations of 0.4 and 0.8 μmol/L were selected for follow-up experiments. EDU-594, Transwell, and flow cytometry showed significantly decreased proliferation and migration rate of K562 cells after 0.4 and 0.8 μmol/L hesperadin treatment for 24 h, and the apoptosis rate was significantly increased compared with the control group ( P<0.05). Western blot indicated a downregulated expression of the antiapoptotic protein Bcl-2 and an elevated expression of proapoptotic proteins Bax and Caspase-3. Moreover, hesperadin increased intracellular lipid peroxidation and Fe 2+ levels compared with the control treatment ( P<0.05). The combination of ferroptosis inhibitor (Fer-1) and hesperadin could reverse the effect of hesperadin on K562 cells. The mRNA and protein levels of ferroptosis-related genes SLC7A11 and GPX4 were significantly decreased in the 0.8 μmol/L hesperadin-treated group ( P<0.05). SLC7A11 overexpression can inhibit hesperadin effect and alleviate ferroptosis. Conclusion:Hesperadin can promote ferroptosis in K562 cells by regulating the SLC7A11/GPX4 axis.
