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2015 ; 10
(7
): e0131946
Nephropedia Template TP
Wittig C
; Scheuer C
; Parakenings J
; Menger MD
; Laschke MW
PLoS One
2015[]; 10
(7
): e0131946
PMID26154255
show ga
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.
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