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Exploring underlying mechanism of artesunate in treatment of acute myeloid leukemia using network pharmacology and molecular docking

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Abstract

Background

Acute myeloid leukemia (AML) is a highly heterogeneous hematological cancer. The current diagnosis and therapy model of AML has gradually shifted to personalization and accuracy. Artesunate, a member of the artemisinin family, has anti-tumor impacts on AML. This research uses network pharmacology and molecular docking to anticipate artesunate potential mechanisms of action in the therapy of AML.

Methods

Screening the action targets of artesunate through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PubChem, and Swiss Target Prediction databases; The databases of Online Mendelian Inheritance in Man (OMIM), Disgenet, GeneCards, and Drugbank were utilized to identify target genes of AML, and an effective target of artesunate for AML treatment was obtained through cross-analysis. Protein–protein interaction (PPI) networks are built on the Cytoscape platform. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the relevant targets using R software. Finally, using molecular docking technology and Pymol, we performed verification of the effects of active components and essential targets.

Results

Artesunate 30 effective targets for treating AML include CASP3, EGFR, MAPK1, and STAT3, four targeted genes that may have a crucial function in disease management. The virus infection-related pathway (HeptatisB (HBV), Human papillomavirus (HPV), Epstein-Barr virus (EBV) infection and etc.), FoxO, viral carcinogenesis, and proteoglycans in cancer signaling pathways have all been hypothesized to be involved in the action mechanism of GO, which is enriched in 2044 biological processes, 125 molecular functions, 209 cellular components, and 106 KEGG pathways. Molecular docking findings revealed that artesunate was critically important in the therapy of AML due to its high affinity for the four primary disease targets. Molecular docking with a low binding energy yields helpful information for developing medicines against AML.

Conclusions

Consequently, artesunate may play a role in multi-targeted, multi-signaling pathways in treating AML, suggesting that artesunate may have therapeutic potential for AML.

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Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.

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Funding

This work was supported by the National Natural Science Foundation of China (No.81873286), Program of Shanghai Academic Research Leader (No.20XD1403500), Shanghai Science Technology and Innovation Action Plan (No.21Y31920400), Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center (No. SHDC12020128).

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Author notes

  1. Yuchen Tao and Wenhang Li authors have contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Yuchen Tao, Tingting Xue, Yanlu Wang, Xiaojie Dong, Hao Xu, Jianye Ren & Jiahui Lu

  2. Meishan Traditional Chinese Medicine Hospital, The Affiliated Meishan Hospital of Chengdu University of Traditional Chinese Medicine, Meishan, Sichuan, China

    Wenhang Li & Jianying Yang

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  1. Yuchen Tao
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Contributions

All authors contributed to the article and approved the submitted version. YT and WL participated in data collection and analysis. JY, TX, YW, XD, HX, and JR participated in manuscript writing. JL is responsible for the integrity and accuracy of the data.

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Correspondence to Jiahui Lu.

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Tao, Y., Li, W., Yang, J. et al. Exploring underlying mechanism of artesunate in treatment of acute myeloid leukemia using network pharmacology and molecular docking. Clin Transl Oncol 25, 2427–2437 (2023). https://doi.org/10.1007/s12094-023-03125-5

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