Transcriptomic Analysis of Colorectal Cancer Cells Treated with Oil Production Waste Products (OPWPs) Reveals Enrichment of Pathways of Mitochondrial Functionality

Abstract

Oil production waste products (OPWPs) derive from olive mill and represent a crucial environmental problem due to their 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 PPARγ mediates the effects as they are mimicked by a specific ligand and impaired by a specific inhibitor. OPWP extracts and hydroxytyrosol, thus, promote mitochondrial functionality via a feed-forward regulatory loop involving the PPARγ/PGC-1α axis. These results support their use in functional foods and as adjuvants in cancer therapy.

B7H4 Expression Is More Frequent in MSS Status Colorectal Cancer and Is Negatively Associated with Tumour Infiltrating Lymphocytes

“…In detail, E2F Target, c-MYC, and G2/M Checkpoint were the first four most impacted and downregulated pathways, suggesting that the main effect is an impaired cell cycle block, in particular a G2/M phase transition arrest. E2F is an essential protein that regulates the cell cycle with a block at the G2/M phase [ 60 , 61 , 62 ]. On the other hand, downregulated c-MYC target pathways could seem contradictory as c-MYC is an oncogene; however, this pathway includes many genes involved in restraining cell growth [ 62 ].…”

“…E2F is an essential protein that regulates the cell cycle with a block at the G2/M phase [ 60 , 61 , 62 ]. On the other hand, downregulated c-MYC target pathways could seem contradictory as c-MYC is an oncogene; however, this pathway includes many genes involved in restraining cell growth [ 62 ]. Functional analyses of B7H4 also confirmed its association with immunological-related processes.…”

Combined SERS-Raman screening of HER2-overexpressing or silenced breast cancer cell lines

“…Protein extracts were analysed as previously reported [ 31 ]. Antibodies to p-HER2 (Y1248 # 2247), HER2 (#3250), p-AKT (S473) (#9271), AKT (#9272) were from Cell Signaling Technology (Beverly, MA USA); α-Tubulin (T5168) was from Sigma-Aldrich Co. (Merck KGaA, St. Louis, MO, USA).…”

Mitochondrial fusion–fission dynamics and its involvement in colorectal cancer

“…Specific compounds, such as oil production waste product (OPWP) extracts, hydroxytyrosol [ 81 ], and the glucose analog 2‐DG [ 82 ], may intervene in colonic tumor growth by promoting mitochondrial fusion into network structures. Mechanistically, OPWP extracts and hydroxytyrosol promote mitochondrial fusion through the PPARγ/PGC‐1α axis and upregulate OXPHOS signaling, ultimately inhibiting cell proliferation and inducing apoptosis [ 81 ]. Tumor cells are known to primarily rely on glycolysis for energy production.…”