Perillyl Alcohol Attenuates in vitro Angiogenesis, Modulates Angiogenic Factor Production and Inhibits Cell Proliferation and Survival in Endothelial and Tumour Cells

Anti-angiogenic therapy is one of the most promising approaches to control cancer. In this work we studied the effects of perillyl alcohol (POH), a dietary monoterpene with in vivo anti-cancer activity on in vitro angiogenesis, expression of angiogenic ligands and cell proliferation/apoptosis using endothelial and tumour cells. We have shown that POH attenuates the capillary-like organization of cultured endothelial cells, decreases the expression of vascular endothelial growth factor (VEGF) by cancer cells, increases the expression of Angiopoietin 2 (Ang2) by endothelial cells and inhibits cell proliferation and survival in both cell types. We have also demonstrated that POH inhibits the phosphorylation of two key signaling molecules: Akt in endothelial cells and Erk1/2 in cancer cells.