Abstract
The traditional medicine Dingqing Tablet produces effective efficacy in treating acute myeloid leukemia, but its specific mechanism remains to be investigated. Dingqing Tablet consists of Codonopsis, Indigo Naturalis, Cortex Moutan, Radix Notoginseng, Citrus Reticulata, and Eolite. The active components of Dingqing Tablets were screened by the TCMSP database. Meanwhile, the SwissTargetPrediction database was utilized to predict the corresponding targets. Relevant disease targets of acute myeloid leukemia were obtained from GeneCards. The obtained targets of Dingqing Tablets and genes of acute myeloid leukemia were used, and the overlapped genes were presented in the Venn diagram. A drug-component-target network was constructed via Cytoscape 3.6.0 software. Molecular docking methodology was also used with AutoDock Vina 1.1.2. Furthermore, the effects of kaempferol on the proliferation and apoptosis of HL-60 cells were identified using 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT), 5-Ethynyl-2′-deoxyuridine (EDU), flow cytometry, and TdT-mediated dUTP nick-end labeling (TUNEL) assays. The combination of kaempferol and AKT1 was verified using an immunoprecipitation (IP) experiment and the effects of Kaempferol on HL-60 cell apoptosis by western blot (WB) and qPCR. The key component kaempferol and the core target gene AKT1 were sorted out using a drug-component target network diagram. Molecular docking results revealed that the binding energy between kaempferol and AKT1 was lower than -5 kcal/mol. MTT and EDU assays indicated that kaempferol markedly inhibited the proliferation of HL-60 cells. Flow cytometry and TUNEL assays suggested that kaempferol substantially promoted HL-60 cell apoptosis. IP assay results testified that kaempferol could bind to AKT1, thereby reducing the level of P-AKT and promoting HL-60 cell apoptosis. The monomer kaempferol of Dingqing Tablet could promote apoptosis of HL-60 cells, and the mechanism might correlate with the combination of kaempferol and AKT1, reducing the level of P-AKT and promoting the expression of the apoptotic signaling pathway.
Highlights
Acute myeloid leukemia (AML) is recognized as a highly heterogeneous disorder and the most common acute leukemia developed in adults [1]. e American Cancer Society’s 2021 estimate of leukemia in the United States is that there will be 20,240 new cases of AML, mostly adults, and about 11,400 deaths from acute myeloid leukemia, almost all of which occur in adults
To explore the actions of Dingqing Tablet on leukemia HL-60 cells, we initially determined the active ingredients and relevant targets of Dingqing Tablets. ere were 707 targets sorted from Dingqing Tablet and 585 targets from human AML (Figure 1(a)). e overlapped genes of Radix Notoginseng, Citrus Reticulata, Codonopsis, Cortex Moutan, Indigo Naturalis, and Eolite and human AML were 37, 6, 97, 15, 102, and 58, respectively (Figure 1(b))
A PPI protein interaction network diagram was constructed through String (Figure 1(c)). e drugs, ingredients, and targets were visualized via Cytoscape 3.6, we found that MDP2, DS6, XH, and E1 were the key ingredients in Dingqing Tablet, and AKT and STAT3 were the core target genes with top degrees (Figure 1(d))
Summary
Acute myeloid leukemia (AML) is recognized as a highly heterogeneous disorder and the most common acute leukemia developed in adults [1]. e American Cancer Society’s 2021 estimate of leukemia in the United States is that there will be 20,240 new cases of AML, mostly adults, and about 11,400 deaths from acute myeloid leukemia, almost all of which occur in adults. Acute myeloid leukemia (AML) is recognized as a highly heterogeneous disorder and the most common acute leukemia developed in adults [1]. E American Cancer Society’s 2021 estimate of leukemia in the United States is that there will be 20,240 new cases of AML, mostly adults, and about 11,400 deaths from acute myeloid leukemia, almost all of which occur in adults. AML is one of the most common types of leukemia in adults. AML is fairly rare overall, accounting for only about 1% of all cancers [2]. It is characterized by an abnormal proliferation of leukemia cells in the bone marrow. Chemotherapy and stem cell transplantation are widely applied in the treatment of AML [4].
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