[Effect and molecular mechanism of hesperadin-induced ferroptosis in chronic myeloid leukemia K562 cells].
Zhonghua Xue Ye Xue Za Zhi
; 45(6): 577-585, 2024 Jun 14.
Article
in Zh
| MEDLINE
| ID: mdl-39134490
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/
Cell Proliferation
/
Ferroptosis
Limits:
Humans
Language:
Zh
Journal:
Zhonghua Xue Ye Xue Za Zhi
Year:
2024
Document type:
Article
Affiliation country:
China