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Lycorine induces apoptosis of acute myeloid leukemia cells and inhibits triglyceride production via binding and targeting FABP5

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Abstract

Acute myeloid leukemia (AML) is the most common hematopoietic malignancy with abnormal lipid metabolism. However, currently available information on the involvement of the alterations in lipid metabolism in AML development is limited. In this study, we demonstrate that FABP5 expression facilitates AML cell viability, protects AML cells from apoptosis, and maintains triglyceride production. Our bioinformatics analysis revealed that FABP5 expression was upregulated and correlated with unfavorable overall survival of AML patients. FABP5 expression may be used to distinguish normal and AML with high accuracy. FABP5-based risk score was an independent risk factor for AML patients. AML patients with highly expressed FABP5 predicted resistance to drugs. In vitro study showed that FABP5 expression was remarkably elevated in primary AML blasts and an AML cell line. Silencing FABP5 expression attenuated AML cell viability, reduced triglyceride production and lipid droplet accumulation, and induced apoptosis. We utilized AutoDock online tool to identify lycorine as an FABP5 inhibitor by binding FABP5 at amino acid residues Ile54, Thr56, Thr63, and Arg109. Lycorine treatment downregulated the expression levels of FABP5 and its target PPARγ, impaired AML cell viability, triggered apoptosis, and reduced triglyceride production in AML cells. These results demonstrate that FABP5 is critical for AML cell survival and highlight a novel metabolic vulnerability for AML.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (31960137, 32260171) and the Guizhou Provincial Natural Science Foundation (Qiankehejichu [2016]1416).

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Author notes

  1. Xinming Liang and Wenli Fu contributed equally to this work

Authors and Affiliations

  1. Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, School of Basic Medical Science, Guizhou Medical University, Guiyang, 550004, Guizhou, China

    Xinming Liang, Wenli Fu, YuHui Peng, Juanjuan Duan, Ting Zhang, Daogui Fan, Wei Hong, Xiaolan Qi, ChangXue Wu, Yan He, Wenfeng Yu & Qifang Zhang

  2. School of Biology and Engineering, Guizhou Medical University, Guiyang, China

    Jing Zhou

  3. Department of Hematology, Guizhou Provincial People’s Hospital, Guizhou University, Guiyang, 550002, Guizhou, China

    Pengxiang Guo

  4. Medical Laboratory Center, the Third Affiliated Hospital of Guizhou Medical University, Duyun, 558000, Guizhou, China

    Hua Bai

  5. Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research On Common Chronic Diseases, Guiyang, 550004, Guizhou, China

    Qifang Zhang

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  1. Xinming Liang
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Contributions

Q.F.Z. and H.B. conceived and designed the study. B.X.G diagnosed AML patients and provided samples. X.M.L., W.L.F., Y.H.P, J.J.D., T.Z, D.G.F., and W.H. obtained and assembled data. X.L.Q., C.X.W., Y.H., and W.F.Y. analyzed and interpreted the data. Y.H. and C.J.W. did the statistical analysis. The paper was written by Q.F.Z. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Pengxiang Guo, Hua Bai or Qifang Zhang.

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Liang, X., Fu, W., Peng, Y. et al. Lycorine induces apoptosis of acute myeloid leukemia cells and inhibits triglyceride production via binding and targeting FABP5. Ann Hematol 102, 1073–1086 (2023). https://doi.org/10.1007/s00277-023-05169-7

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