Itraconazole Modulates Phospholipid Levels in Tumor-associated Macrophages
Anticancer research(2023)
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 mu M 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.
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Key words
Itraconazole,drug repurposing,tumor-associated macrophages
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