Geraniol Suppresses Angiogenesis by Downregulating Vascular Endothelial Growth Factor (VEGF)/VEGFR-2 Signaling.

Abstract

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.

• Authors: Christine Wittig, Claudia Scheuer, Julia Parakenings, Michael D Menger, Matthias W Laschke
• Journal: PloS one (PLoS One) Vol. 10 Issue 7 Pg. e0131946 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26154255 (Publication Type: Journal Article)

Chemical References

• Acyclic Monoterpenes
• Terpenes
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factor Receptor-2
• geraniol

Topics

• Acyclic Monoterpenes
• Animals
• Cell Line
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Down-Regulation (drug effects)
• Hemodynamics (drug effects)
• Humans
• Immunohistochemistry
• In Vitro Techniques
• Male
• Mice, Inbred BALB C
• Microvessels (drug effects, pathology)
• Neoplasms (blood supply, pathology, physiopathology)
• Neovascularization, Pathologic (drug therapy, pathology)
• Neovascularization, Physiologic (drug effects)
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Stress Fibers (drug effects, metabolism)
• Terpenes (pharmacology, therapeutic use)
• Vascular Endothelial Growth Factor A (metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (metabolism)