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

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.

An Extract of Olive Mill Wastewater Downregulates Growth, Adhesion and Invasion Pathways in Lung Cancer Cells: Involvement of CXCR4

“…Quantification of the phenolic presence in A009 extracts was performed using a high-performance liquid chromatography (HPLC) analysis. The abundance of the polyphenols contained in different batches has been shown in a previous publication [10,15,16] and is detailed in Supplementary Table S1 and Supplementary Figure S1.…”

“…The OMWW A009 extracts were provided by the "Azienda Agricola-Fattoria La Vialla", following purification as described below. Four batches from different preparations were characterized for molecular contents [10,15,16], revealing similar molecules (Supplementary Table S1, Figure 1). The two most recent batches produced, termed L3 and L4 respectively, were used in this study.…”

“…The ability of the A009 extracts to interfere with lung cancer cell adhesion was investigated by adhesion assay on fibronectin. Following well coating with 2 µg/mL of fibronectin as in [10]. Then, 2 × 10 4 A549 or H1650 cells/well, pre-treated with A009 extracts or Hyt as above, were seeded on a 48-well plate.…”

“…Hydroxytyrosol (HT) represents the most abundant polyphenol present in olive oil and its beneficial properties, including anti-oxidant [7], anti-apoptotic [8], anti-tumor [3,[9][10][11][12], and anti-inflammatory activities [18], have been largely demonstrated in several in vitro and in vivo studies. Olive oil production generates large volumes of waste material, whose management strongly impacts on production costs and represents a relevant source of environmental pollutants [13,14].…”

“…The chemical characterization of these OMWW extracts revealed that they are largely enriched in soluble polyphenols [17]. Recovering polyphenols from waste material is an approach that we have now established, and the ultra-purified extracts from OMWWs that we termed A009 [10,15,16] have been tested for effects on cancer cells. Here, we explored the potential chemoprevention associated activities of these polyphenol-rich extracts in in vitro models of lung cancer and explored their molecular mechanisms.…”