Abstract
Itraconazole shows anticancer activity in various types of cancer but its underlying mechanism is unclear. We investigated the effect of itraconazole on membrane-associated lipids. To investigate the influences of itraconazole on cholesterol trafficking, cervical cancer CaSki cells were cultured with itraconazole and analyzed by Filipin staining followed by confocal microscopy. Effect on the glycerophospholipid profiles was analyzed by liquid chromatography/mass spectrometry (LC/MS). After itraconazole treatment, Filipin staining revealed cholesterol accumulation in the intracellular compartments, which was similar to the distribution after treatment of U18666A (cholesterol transport inhibitor). LC/MS analysis showed a significant decrease in phosphatidylserine levels and an increase in lysophosphatidylcholine levels in CaSki cells. Itraconazole inhibited cholesterol trafficking and altered the phospholipid composition. Alterations in the cell membrane can potentiate the anticancer activity of itraconazole.
Published Version
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