Effect of Juglone on Proliferation Inhibition and RIPK1/RIPK3/MLKL Expression in Acute Myeloid Leukemia Cells.
10.19746/j.cnki.issn.1009-2137.2025.04.008
- Author:
Chun-Yi LYU
1
;
Xue-Wei YIN
2
;
Zong-Hong LI
1
;
Chen HAN
1
;
Yan WANG
3
;
Zhen-Zhen WANG
3
;
Lyu-Ye LIU
4
;
Rui-Rong XU
3
Author Information
1. The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China.
2. The Laboratory Center, The Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250002, Shandong Province, China.
3. Key Laboratory of Hematology of Integrated Traditional Chinese and Western Medicine of Health Commission of Shandong Province; Institute of Hematology of Shandong University of Traditional Chinese; Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China.
4. Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
- Publication Type:Journal Article
- Keywords:
juglone;
leukemia;
RIPK1/RIPK3/MLKL signaling pathway;
apoptosis
- MeSH:
Humans;
Naphthoquinones/pharmacology*;
Apoptosis/drug effects*;
Cell Proliferation/drug effects*;
Leukemia, Myeloid, Acute/pathology*;
Cell Line, Tumor;
Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*;
Protein Kinases/metabolism*;
Signal Transduction;
Cell Survival/drug effects*
- From:
Journal of Experimental Hematology
2025;33(4):980-985
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia (AML) cells.
METHODS:Juglone and AML targets were collected from public databases, and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML. Then wet experiments were performed to verify. AML cell lines including KG-1a, MV-411, THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h. MTT assay was used to detect cell viability and determine the IC50, and the most sensitive cell line was screened for subsequent experiments. Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone. Western blot was performed to check the expression of relevant proteins.
RESULTS:Eleven targets were obtained as potential targets for juglone in the treatment of AML, and the top ten significantly enriched pathways were intrinsic pathway of apoptosis, programmed cell death, cytochrome c-mediated apoptotic response, apoptosis, apoptotic factor-mediated response, regulated necrosis, cytokine signaling in immune system, signaling by interleukins, oncogene induced senescence, and signal transduction. The cell viability of KG-1a, MV-411, THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment (r =-0.992, -0.886, -0.956, -0.910). Among them, MOLM-13 was the most sensitive to juglone. The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone (r =0.99). At the same time point, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLK were decreased in each juglone concentration group compared with control group.
CONCLUSION:Juglone inhibits the viability of KG-1a, MV-411, THP-1 and MOLM-13 cells, and induces apoptosis of MOLM-13 cells, the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.
