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

Abstract

Several diet-derived compounds have been reported to exert antioxidant, anti-proliferative and anti-angiogenic effects in numerous cancers and could be beneficial in cancer prevention. Olive oil production involves the generation of an aqueous phase defined as olive mill wastewater (OMWW), a polluting effluent rich in soluble polyphenols. Here, we assessed the cancer preventive properties exerted by a purified extract of OMWW (A009) for its activity on lung cancer cell lines. Hydroxytyrosol, the most abundant polyphenol present in our A009 extracts, was used as reference molecule in the assays performed. Extracts from OMWW from two different olive oil cultivars were used. We found that the A009 extracts limit lung cancer cell proliferation in a dose and time dependent manner. These effects were associated with the induction of apoptosis. A009 extracts were effective in inhibiting adhesion capabilities on a fibronectin layer accompanied with a reduction in their ability to generate invasive sprouts in a Matrigel layer. The production of chemokine CXCL12 and CXCR4 receptor were reduced by treatment with the extracts. Also, A009 interfered with the production of proangiogenic and pro-inflammatory VEGF, CXCL8, and CCL2 (as detected by FACS analysis) in the lung cell lines. A009 extracts were able to decrease STAT3 phosphorylation in lung cancer cells. Our results show that A009 extracts reduced activities related to tumor cell behavior in lung cancer cell lines, suggesting that they could have a potential cancer preventive role.

Olive Mill Wastewater Inhibits Growth and Proliferation of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro by Down-Regulating the Akt/mTOR-Signaling Pathway

“…Depending on the cell line and resistance to cisplatin or gemcitabine, OMWW was effective at dilutions ranging from 1:125 to 1:500. This agrees with another experimental model, where OMWW at a dilution ranging from 1:50 to 1:250 significantly blocked the growth of lung cancer cell lines [20]. The same efficacy was seen with DU145 and PC3 prostate cancer cells, whereby the growth of the prostate cancer cell line LNCaP was already blocked by an OMWWdilution of 1:5000 [19].…”

“…OMWW is generated during olive oil production, and chemical characterization of OMWW extracts reveal enrichment with soluble polyphenols, of which hydroxytyrosol (HT) is the most bioactive component [17]. Besides antioxidant actions of OMWW verified in healthy volunteers [18], OMWW has been shown to suppress angiogenesis in a prostate cancer cell model [19] and to down-regulate growth and invasive properties of lung cancer cells [20]. The relevance of OMWW for drug-resistant tumor cells has not yet been explored.…”

Nutraceuticals and Cancer: Potential for Natural Polyphenols

“…Belonging to the secoiridoids, a group of compounds found exclusively in all 500 species of Oleaceae plants, oleuropein results in a reduction of cell proliferation mainly by using two mechanisms: on the one hand, it acts by stopping the cell cycle through the upregulation of cyclin-dependent kinase (CDK) inhibitors, and on the other, by modulating the genic expression responsible for the induction of intrinsic and extrinsic pathways of apoptosis through the upregulation of p53 and p21. In addition, oleuropein can alter the function of key molecules involved in the onset and development of cancer such as MAPKs, c-Met proto-oncogene, and the fatty acid synthase (FASN) enzyme [131]. A recent study [132] conducted in vitro on two genetically different triplenegative breast cancer (TNBC) cell lines (MDA-MB-231 and MDA-MB-468) demonstrated the ability of oleuropein to suppress cell proliferation, stimulate apoptosis through S-phase cell cycle arrest, and express the initiating caspases of the apoptotic process (Caspase1, 4, and 14).…”

A Polyphenol-Rich Extract of Olive Mill Wastewater Enhances Cancer Chemotherapy Effects, While Mitigating Cardiac Toxicity

“…Here, we investigate the potential cardioprotective activities of a polyphenol-rich, EVOO-derived polyphenol extracts (A009), derived from olive mill wastewater (OMWW). A009-extracts have been reported to exhibit chemopreventive and angiopreventive properties, in vitro and in vivo , in different cancer types ( Baci et al, 2019 ; Gallazzi et al, 2020 ).…”