Comparison of the anti-angiogenic potential of hydroxytyrosol and five derivatives

Hydroxytyrosol is a phenolic compound present in extra virgin olive oil, either in free form or as derivatives, and related to some of the health benefits described for olive oil intake. We have demonstrated previously that hydroxytyrosol inhibits angiogenesis both in vitro and in vivo. In the present study, we evaluate the anti-angiogenic potential of five hydroxytyrosol derivatives. Three of these derivatives contain a nitro group and they exhibit a much weaker effect than hydroxytyrosol in the tubule formation assay on Matrigel and therefore were not studied further. In contrast, both hydroxytyrosyl acetate and ethyl hydroxytyrosyl ether show more potent inhibitory effects than hydroxytyrosol in both the in vitro tubule formation assay on Matrigel and the in vivo chorioallantoic membrane assay. Additionally, these three compounds had slight pro-apoptotic effects and decreased matrix metalloproteinase-2 levels in cell extracts.This work was supported by grants BIO2014-56092-R (MINECO and FEDER), and P12-CTS-1507 and P09-AGR-5098 (Andalusian Government and FEDER). E. G. thanks Junta de Andalucía for a predoctoral fellowship. The “CIBER de Enfermedades Raras” is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript