Evaluation of the anti-angiogenic potential of hydroxytyrosol and tyrosol, two bio-active phenolic compounds of extra virgin olive oil, in endothelial cell cultures

Hydroxytyrosol and tyrosol are phenolic compounds found in virgin olive oil. A number of health-related properties have been previously demonstrated for both. The aim of this study was to investigate the potential anti-angiogenic effects of these compounds. Three different types of endothelial cells were used in several in vitro assays designed to test the specific effects of tested compounds on different key steps of the angiogenic process. Only hydroxytyrosol (but not tyrosol) had significant inhibitory effects on endothelial cell proliferation, migration and “tubule-like” structure formation on Matrigel. Furthermore, hydroxytyrosol changed endothelial cell cycle distribution, with a remarkable increase of subG1 subpopulation, indicative of apoptotic cells. Finally, hydroxytyrosol also behaved as a potent inhibitor of the invasive potential of endothelial cells, as revealed by decreased matrix metalloproteinase 2 in conditioned media. For the first time, this study shows that only hydroxytyrosol (but not tyrosol) is a new multi-targeted anti-angiogenic compound.