2. Academic Validation
  3. Jaceosidin, a natural polymethoxyflavone, suppresses leukemia cell growth and impairs lipid metabolism-dependent survival in AML and cytarabine-resistant cells

Jaceosidin, a natural polymethoxyflavone, suppresses leukemia cell growth and impairs lipid metabolism-dependent survival in AML and cytarabine-resistant cells

  • Biomed Pharmacother. 2025 Oct 19:192:118654. doi: 10.1016/j.biopha.2025.118654.
Trung Q Phan 1,  Je-Wen Liou 2,  Liang-In Lin 3,  Wei-Han Huang 4,  Ming-Jiuan Wu 5,  Pei-Yi Chen 6,  Jui-Hung Yen 7
Affiliations

Affiliations

  • 1 Institute of Medical Sciences, Tzu Chi University, Hualien 970374, Taiwan.
  • 2 Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 970374, Taiwan.
  • 3 Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei City 10048, Taiwan.
  • 4 Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970374, Taiwan; Department of Clinical Pathology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970374, Taiwan; School of Medicine, Tzu Chi University, Hualien 970374, Taiwan.
  • 5 Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 717301, Taiwan.
  • 6 Laboratory of Medical Genetics, Genetic Counseling Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970374, Taiwan; Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970374, Taiwan. Electronic address: pyc571@gms.tcu.edu.tw.
  • 7 Institute of Medical Sciences, Tzu Chi University, Hualien 970374, Taiwan; Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970374, Taiwan. Electronic address: imyenjh@gms.tcu.edu.tw.
PMID: 41115391 DOI: 10.1016/j.biopha.2025.118654
Abstract

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by uncontrolled proliferation of myeloid precursors and frequent chemotherapy resistance. Jaceosidin (Jace), a polymethoxyflavone with antioxidant and Anticancer properties, has not yet been investigated for its therapeutic potential in AML. In this study, we aimed to assess the anti-leukemic potential of Jace using AML cell lines, cytarabine-resistant sublines, patient-derived samples, and zebrafish xenograft models. Jace significantly reduced the viability of AML cells, selectively targeting leukemic cells while sparing normal peripheral blood mononuclear cells (PBMCs). In both MV4-11 and cytarabine-resistant MV4-11 CR cells, Jace inhibited cell growth by suppressing proliferation, inducing G1-phase cell cycle arrest, and promoting monocytic differentiation. Jace markedly reduced leukemia burden in zebrafish xenograft models without causing cardiac toxicity, indicating a favorable in vivo safety profile. Transcriptomic profiling showed that Jace altered multiple gene sets and biological pathways, notably those related to immune regulation, Cholesterol homeostasis, sterol and lipid metabolism, cell cycle progression, cell division, and cell growth. Notably, Jace markedly downregulated genes involved in Cholesterol and fatty acid metabolism, reducing intracellular Cholesterol and triglyceride levels. Supplementation with external lipids restored cell viability, indicating Jace may disrupt lipid-dependent survival in leukemia cells. Moreover, Jace acted synergistically with cytarabine, venetoclax, and midostaurin to enhance cytotoxicity in AML cells. These findings identify Jace as a novel modulator of lipid metabolism with potent anti-leukemic activity and support its potential use as a chemotherapeutic agent in AML treatment strategies.

Keywords

AML; Cytarabine; Jaceosidin; Lipid metabolism; Polymethoxyflavone; Zebrafish xenografts.

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