Lyu Chun-Yi, Yin Xue-Wei, Li Zong-Hong, Han Chen, Wang Yan, Wang Zhen-Zhen, Liu Lyu-Ye, Xu Rui-Rong
The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China.
The Laboratory Center, The Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250002, Shandong Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):980-985. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.008.
To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia (AML) cells.
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 IC, 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.
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 ( =-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 ( =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.
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.
研究胡桃醌对急性髓系白血病（AML）细胞增殖和凋亡的影响及其机制。
从公共数据库收集胡桃醌和AML靶点，对交集靶点聚类进行功能富集分析，以探索胡桃醌治疗AML的潜在机制。然后进行湿实验验证。用不同浓度的胡桃醌处理包括KG-1a、MV-411、THP-1和MOLM-13在内的AML细胞系24小时。采用MTT法检测细胞活力并确定IC，筛选出最敏感的细胞系用于后续实验。用流式细胞术检测不同浓度胡桃醌处理的细胞凋亡情况。进行蛋白质免疫印迹法检测相关蛋白的表达。
获得11个靶点作为胡桃醌治疗AML的潜在靶点，前十大显著富集通路为凋亡内在途径、程序性细胞死亡、细胞色素c介导的凋亡反应、凋亡、凋亡因子介导的反应、调节性坏死、免疫系统中的细胞因子信号传导、白细胞介素信号传导、癌基因诱导的衰老和信号转导。胡桃醌处理24小时后，随着胡桃醌浓度增加，KG-1a、MV-411、THP-1和MOLM-13的细胞活力降低（r=-0.992、-0.886、-0.956、-0.910）。其中，MOLM-13对胡桃醌最敏感。流式细胞术结果显示，随着胡桃醌浓度增加，MOLM-13的凋亡率显著升高（r=0.99）。在同一时间点，各胡桃醌浓度组的p-RIPK1/RIPK1、p-RIPK3/RIPK3和p-MLKL/MLK均低于对照组。
胡桃醌抑制KG-1a、MV-411、THP-1和MOLM-13细胞活力，诱导MOLM-13细胞凋亡，其机制可能与抑制RIPK1/RIPK3/MLKL信号通路有关。
