Polyphenols Extracts from Oil Production Waste Products (OPWPs) Reduce Cell Viability and Exert Anti-Inflammatory Activity via PPAR gamma Induction in Colorectal Cancer Cells

Olive oil production is associated with the generation of oil production waste products (OPWPs) rich in water-soluble polyphenols that represent serious environmental problems. Yet OPWPs can offer new opportunities by exploiting their bioactive properties. In this study, we chemically characterized OPWPs polyphenolic extracts and investigated their biological activities in normal and colorectal cancer cells. Hydroxytyrosol (HTyr), the major constituent of these extracts, was used as the control. We show that both HTyr and the extracts affect cell viability by inducing apoptosis and cell cycle arrest. They downregulate inflammation by impairing NF-kappa B phosphorylation and expression of responsive cytokine genes, as TNF-alpha and IL-8, at both mRNA and protein levels, and prevent any further increase elicited by external challenges. Mechanistically, HTyr and the extracts activate PPAR gamma while hampering pro-inflammatory genes expression, acting as a specific agonist, likely through a trans-repression process. Altogether, OPWPs polyphenolic extracts show stronger effects than HTyr, conceivably due to additive or synergistic effects of all polyphenols contained. They display anti-inflammatory properties and these results may pave the way for improving OPWPs extraction and enrichment methods to reduce the environmental impact and support their use to ameliorate the inflammation associated with diseases and tumors.