3RD PLACE, ORIGINAL RESEARCH TRACK: Integrative lipidomics and network pharmacology reveal the mechanisms of cannabidiol in the treatment of acute myeloid leukemia

Dysregulated lipid metabolism contributes significantly to the development of acute myeloid leukemia (AML), a rare hematologic malignancy with limited therapeutic options. Cannabidiol (CBD) shows promise in lipid modulation and tumor suppression and may offer therapeutic effects for lipid-mediated cancers. This study identifies lipid biomarkers and molecular targets linked with CBD treatment in AML using an integrative lipidomics and network pharmacology approach. Liquid chromatography-mass spectrometry (LC-MS) datasets were retrieved from Metabolomics Workbench and analyzed through multivariate, univariate, and chemometric analyses. Significantly altered lipid species were mapped to metabolic pathways, and network pharmacology identified CBD targets involved in tumor suppression and lipid modulation. Sphingolipid, glycerophospholipid, and linoleic acid metabolisms were the most enriched pathways. PI (32:2), PC (28:1), PC (39:2), TG (46:2), and LPC (26:0) emerged as key lipid biomarkers of CBD treatment. Network analysis identified 88 overlapping targets between CBD and AML-associated genes, with enrichment in the neuroactive ligand-receptor pathway, calcium signaling pathway, and membrane function pathways. Three hub genes were identified as key mediators of CBD-treatment: COMT, ALB, and CYP3A4. The integrative analysis revealed CBD may inhibit CYP3A4 in the linoleic acid metabolism, leading to PC accumulation and subsequent stress signaling that triggers apoptosis in AML cells. These results provide insight into the mechanisms of CBD in AML and support its therapeutic role in targeting dysregulated lipid metabolism.