Network Pharmacology and In Vitro Experiments Reveal the Mechanism of Agaricus blazei Murill Extract in Treating Chronic Myeloid Leukemia

Chem Biodivers. 2025 Nov;22(11):e00758. doi: 10.1002/cbdv.202500758. Epub 2025 Jul 26.

Abstract

Chronic myeloid leukemia (CML) is a malignant hematological neoplasm. FA-2-b-β, extracted from Agaricus blazei Murrill, has demonstrated antitumor activity against multiple cancer types. Nevertheless, the specific pharmacodynamic components and molecular mechanisms of FA-2-b-β against CML remain to be elucidated. This study aimed to systematically investigate the mechanism of FA-2-b-β against CML through an integrated strategy combining liquid chromatography-tandem mass spectrometry (LC-MS/MS), network pharmacology prediction, and in vitro experimental validation. Using LC-MS/MS profiling, we identified a total of 126 chemical components. Subsequently, network pharmacological analysis screened 45 potentially active components and 129 CML-related overlapping targets. Further pathway enrichment analysis revealed that these candidate targets were predominantly involved in the PI3K/AKT and MAPK pathways. In vitro validation confirmed the suppression of PI3K/AKT phosphorylation in K562 cells. Collectively, this study provides significant insights into the active components and antitumor mechanisms of FA-2-b-β, emphasizing its potential as a promising therapeutic agent for treating CML.

Keywords: FA‐2‐b‐β; chronic myeloid leukemia; experimental validation; liquid chromatography–tandem mass spectrometry (LC–MS/MS); network pharmacology.

MeSH terms

  • Agaricus* / chemistry
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / isolation & purification
  • Antineoplastic Agents* / pharmacology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chromatography, Liquid
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / pathology
  • Molecular Structure
  • Network Pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Tandem Mass Spectrometry

Substances

  • Antineoplastic Agents
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt