2. Academic Validation
  3. Lycorine eliminates B-cell acute lymphoblastic leukemia cells by targeting PSAT1 through the serine/glycine metabolic pathway

Lycorine eliminates B-cell acute lymphoblastic leukemia cells by targeting PSAT1 through the serine/glycine metabolic pathway

  • Eur J Pharmacol. 2023 Nov 10:961:176162. doi: 10.1016/j.ejphar.2023.176162.
Yong Liu 1,  Zefan Du 2,  Tianwen Li 2,  Jing Zhang 3,  Yucai Cheng 2,  Junbing Huang 2,  Jing Yang 2,  Luping Wen 4,  Mengyao Tian 2,  Mo Yang 5,  Chun Chen 6
Affiliations

Affiliations

  • 1 Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, China; Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, China.
  • 2 Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, China.
  • 3 Department of Breast and Thyroid Surgery, Guangzhou Women and Children's Medical Center, 510623, Guangzhou, China.
  • 4 Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, China.
  • 5 Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, China. Electronic address: yangm1091@126.com.
  • 6 Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, China. Electronic address: chenchun@mail.sysu.edu.cn.
PMID: 37951487 DOI: 10.1016/j.ejphar.2023.176162
Abstract

B-cell acute lymphoblastic leukemia (B-ALL) has been confirmed as the most common malignant hematologic neoplasm among children. A novel antitumor mechanism of lycorine was elucidated in this study. As revealed by the result of this study, lycorine significantly inhibited the growth and proliferation of REH and NALM-6 and induced their Apoptosis. The result of the RNA-seq analysis suggested that lycorine targeted PSAT1 of serine/glycine metabolism in B-ALL cells. As indicated by the result of the GSEA analysis, the genes enriched in the amino acid metabolic pathways were down-regulated by lycorine. As revealed by the results of ectopic expression, shRNA knockdown assays, and further liquid-phase tandem mass spectrometry (LC-MS) analysis, lycorine reduced serine/glycine metabolites by down-regulating PSAT1, further disrupting carbon metabolism and eliminating B-ALL cells. Furthermore, lycorine showed a synergistic effect with cytarabine in ALL treatments. Lastly, lycorine significantly down-regulated leukemia progression in the cell line-derived xenograft (CDX) model. In brief, this study has suggested for the first time that lycorine is a promising anti-ALL drug, and a novel amino acid metabolism-associated property of lycorine was identified.

Keywords

Acute lymphoblastic leukemia; Lycorine; Metabolism; PSAT1; Serine.

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