Itraconazole inhibits HMEC-1 angiogenesis

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Renata Del CarratoreSilvana Balzan

Abstract

Abnormal angiogenesis is implicated in a number of human diseases and endothelial growth inhibition represents a common approach in tumor therapy. Recently itraconazole, frequently used in humans as antifungal drug, which blocks the biosynthesis of cholesterol, has been found to be antiangiogenic in primary umbilical vein endothelial cells. However, the exact antiangiogenic mechanisms remain largely unknown. In this paper, we studied the effect of itraconazole in human dermal microvascular endothelial cells (HMEC-1), an immortalized cell line to study adult angiogenesis. A 50% reduction of microtubule formation was observed after itraconazole treatment which was partially rescued by cholesterol addition. We found that itraconazole inhibits angiogenesis markers such as VEGF, AAMP and e-NOS. mTOR and ERK1/2 phosphorylation as well as the expression of Gli1, one of the main controllers of the Shh pathway, were also inhibited by itraconazole. Cholesterol addition did not completely rescue inhibition of these pathways, suggesting that the itraconazole antiangiogenic activity could be due to multiple mechanisms. Our results may contribute to novel approaches to block angiogenesis with therapeutic application.

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Citations

Dec 17, 2014·The Journal of Dermatology·Yuping RanKaiwen Zhuang
Jun 13, 2015·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Chiara GiorgiFrancesca Vaglini
Jan 23, 2016·PloS One·Xiangli YeYuequn Wang
Jan 31, 2017·Biochemical Pharmacology·Katharina R BeckAlex Odermatt
Apr 17, 2013·International Journal of Oncology·Ruiliang GeYi Wang
Aug 4, 2020·Bioorganic Chemistry·Christophe GuillonJeffrey D Laskin
Apr 17, 2020·ACS Pharmacology & Translational Science·Michael L GareljaDebbie L Hay

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