Downregulation of Pro-Inflammatory and Pro-Angiogenic Pathways in Prostate Cancer Cells by a Polyphenol-Rich Extract from Olive Mill Wastewater.

Denisa Baci,Matteo Gallazzi,Douglas Noonan,Adriana Albini,Matilde Tramacere,Antonino Bruno,Caterina Cascini,Daniela De Stefano

doi:10.3390/ijms20020307

Abstract

Dietary phytochemicals are particularly attractive for chemoprevention and are able to modulate several signal transduction pathways linked with cancer. Olive oil, a major component of the Mediterranean diet, is an abundant source of phenolic compounds. Olive oil production is associated with the generation of a waste material, termed ‘olive mill wastewater’ (OMWW) that have been reported to contain water-soluble polyphenols. Prostate cancer (PCa) is considered as an ideal cancer type for chemopreventive approaches, due to its wide incidence but relatively long latency period and progression time. Here, we investigated activities associated with potential preventive properties of a polyphenol-rich olive mill wastewater extract, OMWW (A009), on three in vitro models of PCa. A009 was able to inhibit PCa cell proliferation, adhesion, migration, and invasion. Molecularly, we found that A009 targeted NF-κB and reduced pro-angiogenic growth factor, VEGF, CXCL8, and CXCL12 production. IL-6/STAT3 axis was also regulated by the extract. A009 shows promising properties, and purified hydroxytyrosol (HyT), the major polyphenol component of A009, was also active but not always as effective as A009. Finally, our results support the idea of repositioning a food waste-derived material for nutraceutical employment, with environmental and industrial cost management benefits.

Highlights

Adherence to a Mediterranean dietary pattern has generally been associated with a decreased risk of developing most non-communicable diseases, including cardiovascular, neurodegenerative pathologies, and cancer [1,2,3,4]
We previously reported that a polyphenol-rich purified extract from olive mill wastewater’ (OMWW), termed A009, which is rich in hydroxytyrosol (HyT), determines anti-angiogenic effects both in endothelial cells in vitro and in an angiogenesis model in vivo [18]
We have shown that a polyphenol-rich OMWW extract, A009, interferes with the angiogenic process in endothelial cells in vitro and in vivo [18,19]

Summary

Introduction

Adherence to a Mediterranean dietary pattern has generally been associated with a decreased risk of developing most non-communicable diseases, including cardiovascular, neurodegenerative pathologies, and cancer [1,2,3,4] This has led to active exploration of whole and isolated products from different naturally occurring sources in various preclinical and clinical settings [5,6,7,8,9]. Extra virgin olive oil (EVOO) is the fresh olive juice obtained exclusively by mechanical and physical processes of olive extraction It consists of a major fraction of triacylglycerides representing more than 98% of the total weight, whereas the minor fraction (approximately 2% of the weight) is represented by of a complex set of compounds, which includes over 230 molecules. Current data strongly support the fact that the beneficial effects of olive oil consumption are due to its minor bioactive components [14]

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Conclusion