Transcriptomic analysis of colorectal cancer cells treated with Oil Production Waste Products (OPWPs) reveals enrichment of pathways of mitochondrial functionality

Oil Production Waste Products (OPWPs) derive from olive mill and represent a crucial environmental problem due to the high polyphenolic content able to pollute the ground. One option to reduce the OPWPs’ environmental impact is to exploit polyphenols biological properties. We sought to analyze the transcriptomic variations of colorectal cancer cells exposed to the OPWPs extracts and hydroxytyrosol, the major component, to recognize unknown and ill-defined characteristics. Among the top affected pathways identified by GSEA, we focused on oxidative phosphorylation in an in vitro system. Colorectal cancer HCT116 and LoVo cells treated with hydroxytyrosol or OPWPs extracts showed enhancement of the respiratory chain complexes protein levels, ATP production and membrane potential, suggesting stimulation of mitochondrial functions. The major proteins involved in mitochondrial biogenesis and fusion events of mitochondrial dynamics were positively affected, as by western blot, fostering increase of the mitochondrial mass organized in a network of elongated organelles. Mechanistically, we proved that PPAR mediates the effects as they are mimicked by a specific ligand and impaired by its inhibition. OPWPs extracts and hydroxytyrosol, thus, promote mitochondrial functionality via a feed-forward regulatory loop involving the PPAR/PGC-1 axis. These results support their use in functional foods and as adjuvants in cancer therapy. In all experiments, HCT116 cells were treated with 0.0154 mg mL−1 HTyr or 0.0154 mg mL−1 OPWPs extracts for 72 h; LoVo cells were treated with 0.0231 mg mL−1 HTyr or 0.0231 mg mL−1 OPWPs extracts for 72 h