Study on the apoptosis-inducing effect of esculetin on acute myeloid leukemia HL-60 cells via regulating the AKT/SKP2/MTH1 pathway
- VernacularTitle:秦皮乙素调控AKT/SKP2/MTH1通路诱导急性髓系白血病HL-60细胞凋亡的作用研究
- Author:
Weihua SONG
1
;
Fuying CHU
1
;
Wei XIE
1
;
Jinliang CHEN
2
;
Ping ZHAO
1
;
Hong QIU
3
;
Jian TAO
4
;
Xiang CHEN
1
Author Information
1. Dept. of Laboratory，Nantong First People’s Hospital，Southeast University，Jiangsu Nantong 226001，China
2. Dept. of Respiratory，Nantong First People’s Hospital，Southeast University，Jiangsu Nantong 226001，China
3. Dept. of Pharmacy，Nantong First People’s Hospital，Southeast University，Jiangsu Nantong 226001，China
4. Dept. of Hematology，Nantong First People’s Hospital，Southeast University，Jiangsu Nantong 226001，China
- Publication Type:Journal Article
- Keywords:
esculetin;
acute myeloid leukemia;
HL-60 cells;
protein kinase B;
cell apoptosis;
AKT/SKP2/MTH1 pathway
- From:
China Pharmacy
2026;37(1):36-41
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.
