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Updated: May 22, 2026
09:17
Characterization of the Effects of Migrastatic Inhibitors on 3D Tumor Spheroid Invasion by High-resolution Confocal Microscopy
Published on: September 16, 2019
Itraconazole inhibits HMEC-1 angiogenesis
Renata Del Carratore1, Angelo Carpi, Pascale Beffy
1Institute of Clinical Physiology, National Research Council-CNR, Via Moruzzi 1, Pisa 56124, Italy. rdc@ifc.cnr.it
Summary
Itraconazole, an antifungal drug, inhibits angiogenesis by reducing microtubule formation and key signaling pathways. Cholesterol addition partially reverses these effects, suggesting multiple antiangiogenic mechanisms.
Area of Science:
- Cell Biology
- Biochemistry
- Pharmacology
Background:
- Abnormal angiogenesis is linked to human diseases, with endothelial growth inhibition a key cancer therapy strategy.
- Itraconazole, an antifungal, exhibits antiangiogenic properties by inhibiting cholesterol biosynthesis, but its mechanisms are unclear.
Purpose of the Study:
- To investigate the antiangiogenic mechanisms of itraconazole in human dermal microvascular endothelial cells (HMEC-1).
- To explore the role of cholesterol in itraconazole's antiangiogenic effects.
Main Methods:
- Treatment of HMEC-1 cells with itraconazole.
- Assessment of microtubule formation, angiogenesis markers (VEGF, AAMP, e-NOS), and signaling pathway activation (mTOR, ERK1/2, Gli1).
- Evaluation of the effect of cholesterol addition on itraconazole-induced inhibition.
Main Results:
- Itraconazole reduced microtubule formation by 50%, partially rescued by cholesterol.
- Inhibition of angiogenesis markers VEGF, AAMP, and e-NOS.
- Suppression of mTOR and ERK1/2 phosphorylation and Gli1 expression, with incomplete rescue by cholesterol.
Conclusions:
- Itraconazole exhibits antiangiogenic activity through multiple mechanisms, including effects on microtubule formation and key signaling pathways.
- These findings suggest potential therapeutic applications for itraconazole in blocking angiogenesis.
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