RRC ID 78622
Author Takimoto Y, Tsubamoto H, Isono-Taniguchi R, Ueda T, Sakata K, Nakagawa K, Narita S, Wakimoto YU, Shibahara H, Nishiumi S.
Title Itraconazole Modulates Phospholipid Levels in Tumor-associated Macrophages.
Journal Anticancer Res
Abstract BACKGROUND/AIM:Itraconazole, an antifungal drug, repolarizes pro-tumorigenic M2 tumor-associated macrophages to anti-tumorigenic M1-like phenotypes, thereby inhibiting the proliferation of cancer cells; however, the underlying mechanism remains unclear. Therefore, we investigated the effect of itraconazole on membrane-associated lipids in tumor-associated macrophages (TAM).
MATERIALS AND METHODS:M1 and M2 macrophages were derived from the human monocyte leukemia cell line (THP-1) and cultured with or without 10 μM itraconazole. Cells were homogenized and subjected to liquid chromatography/mass spectrometry (LC/MS) analysis to estimate the glycerophospholipid levels in the cells.
RESULTS:Lipidomic analysis results, displayed on a volcano plot, revealed that itraconazole-induced altered phospholipid composition, with more pronounced changes in M2 macrophages than in M1. Notably, itraconazole significantly increased intracellular phosphatidylinositol and lysophosphatidylcholine levels in M2 macrophages.
CONCLUSION:Itraconazole modulates the lipid metabolism of TAMs, which could have implications for the development of novel cancer therapies.
Volume 43(5)
Pages 1981-1984
Published 2023-5-1
DOI 10.21873/anticanres.16358
PII 43/5/1981
PMID 37097657
MeSH Cell Differentiation Cell Line, Tumor Humans Itraconazole* / pharmacology Macrophages / metabolism Phospholipids / metabolism Phospholipids / pharmacology Tumor Microenvironment Tumor-Associated Macrophages*
Human and Animal Cells THP-1