The presence of diverse phenolic molecules in dietary elements, has been shown to prevent the occurrence of a variety of chronic and inflammatory diseases. Olives and extra virgin oil, a basic component of mediterranean diet represent an important source of these poliphenols, including hydroxytyrosol. While the strong antioxidant potential of these molecules has extensively investigated, their anti-angiogenic and chemopreventive activities remain unknown. Here we assessed the anti-angiogenic and chemopreventive activities exerted by an extracts from olive mill wastewaters (OMWWs), termed A009, which represent a waste product from olive oil industry, in vitro and in vivo on endothelial and different tumour cell lines, as compared with hydroxytyrosol alone

The ability of A009 to affect cell proliferation and survival was evaluated on human umbelical endothelial vein cells (HUVECs), six different tumor cell lines, MCF-7 and MDA-MB-231 (breast), HT-29 and HCT-116 (colon) PC-3 and DU-145 (prostate) and the murine CT26 CRC cells by MTT assay, while the induction of apoptosis and reactive oxygen species (ROS) were assessed by flow cytometry. Functional studies evaluated the capacity of OMWWs to interfere with endothelial cell tube formation, migration and invasion by morphogenesis and Boyden chamber assays, respectively. Finally, the inhibition of angiogenesis and tumor cell growth was evaluated in vivo, by the matrigel sponge assay and tumor xenograft.

The A009 extract was able to inhibit both HUVECs and tumor cell lines growth in a dose dependent manner, exerting a stronger inhibitory effect as compared to the pure hydroxytyrosol alone. This effect was directly associated with the induction of apoptosis and ROS on HUVECs. HT-29 anc HCT-116 CRC cell lines exposed to A009 decreased thei ability to release VEGF and IL-8. Functional studies of HUVECs exposed to A009 demostrated impaired migratory and invasive abilities as far as reduced capability to form capillary-lile-structure in a dose dependent manner. Finally, A009s interfered with angiogenesis and CT26 tumor cell growth in vivo.

Our results suggest that the polyphenol enriched extracts from olive oil processing (OMWWs) A009, show promising angio-preventive and chemo-preventive potentials. In particular, our data demonstrate that a pool of specific polyphenols are characterized by stronger anti-angiogenic/anti-tumor properties compared to hydroxytyrosol alone, a well known polyphenol with anti-tumor activity.

Citation Format: Adriana Albini, Antonino Bruno, Barbara Bassani, Nicoletta Macrì, Francesca Caudano, Paola Corradino, Teresa Rossi, Douglas M. Noonan. Chemopreventive and angiopreventive activity of a purified polyphenol-rich extract from olive mill wastewaters. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5262.