Geraniol exerts several direct pharmacological effects on
tumor cells and, thus, has been suggested as a promising anti-
cancer compound. Because vascularization is a major precondition for
tumor growth, we analyzed in this study the anti-angiogenic action of
geraniol. In vitro,
geraniol reduced the migratory activity of endothelial-like eEND2 cells. Western blot analyses further revealed that
geraniol downregulates
proliferating cell nuclear antigen (
PCNA) and upregulates cleaved
caspase-3 (Casp-3) expression in eEND2 cells. Moreover,
geraniol blocked
vascular endothelial growth factor (
VEGF)/VEGFR-2 signal transduction, resulting in a suppression of downstream AKT and ERK signaling pathways. In addition,
geraniol significantly reduced vascular sprout formation in a rat aortic ring assay. In vivo,
geraniol inhibited the vascularization of CT26
tumors in dorsal skinfold chambers of BALB/c mice, which was associated with a smaller
tumor size when compared to vehicle-treated controls. Immunohistochemical analyses confirmed a decreased number of Ki67-positive cells and CD31-positive microvessels with reduced
VEGFR-2 expression within
geraniol-treated
tumors. Taken together, these findings indicate that
geraniol targets multiple angiogenic mechanisms and, therefore, is an attractive candidate for the anti-angiogenic treatment of
tumors.