Cedrol is a
sesquiterpene alcohol isolated from Cedrus atlantica, which has been traditionally used in
aromatherapy and has anticancer, antibacterial and antihyperalgesic effects. One characteristic of
glioblastoma (GB) is the overexpression of
vascular endothelial growth factor (
VEGF), which induces a high degree of angiogenesis. Although previous studies have reported that
cedrol inhibits GB growth by inducing DNA damage, cell cycle arrest and apoptosis, its role in angiogenesis remains unclear. The aim of the present study was to investigate the effects of
cedrol on
VEGF-induced angiogenesis of human umbilical vein endothelial cells (HUVECs). HUVECs were treated with 0-112 µM
cedrol and 20 ng/ml
VEGF for 0-24 h, and then anti-angiogenic activation of
cedrol was determined by MTT assay, wound healing assay, Boyden chamber assay, tube formation assay, semi-quantitative reverse transcription-PCR and western blotting. These results demonstrated that
cedrol treatment inhibited
VEGF-induced cell proliferation, migration and invasion in HUVECs. Furthermore,
cedrol prevented
VEGF and DBTRG-05MG GB cells from inducing capillary-like tube formation in HUVECs and decreased the number of branch points formed. Moreover,
cedrol downregulated the phosphorylation of
VEGF receptor 2 (VEGFR2) and the expression levels of its downstream mediators AKT, ERK,
VCAM-1,
ICAM-1 and MMP-9 in HUVECs and DBTRG-05MG cells. Taken together, these results demonstrated that
cedrol exerts anti-angiogenic effects by blocking VEGFR2 signaling, and thus could be developed into health products or therapeutic agents for the prevention or treatment of
cancer and angiogenesis-related diseases in the future.