Publications

Authors:

Leo, Manuela; Mancini, Caterina; Lori, Giulia; Delre, Pietro; Ferraris, Irene; Lucchini, Filippo; Molinario, Annamaria; Leri, Manuela; Castellaneta, Andrea; Losito, Ilario; Cataldi, Tommaso; Rossato, Marzia; Colantuoni, Vittorio; Taddei, Maria Letizia; Lavecchia, Antonio; Sabatino, Lina

Title:

Secoiridoid-enriched extra virgin olive oil extracts enhance mitochondrial activity and antioxidant response in colorectal cancer cells: The role of Oleacein and Oleocanthal in PPARγ interaction

Year:

2025

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

Free Radical Biology and Medicine

ISSN of journal:

0891-5849

N° Volume:

235

Page numbers:

56-72

Keyword:

Antioxidant response; Mitochondria metabolism; Molecular docking; Oleacein; Oleocanthal; PPARγ; Secoiridoids

Short description of contents:

The secoiridoid-enriched fraction of extra virgin olive oil (EVOO) provides significant health benefits, but its underlying mechanisms have not been fully elucidated. To investigate this, we analyzed the transcriptome of HCT116 colorectal cancer cells treated with secoiridoid-enriched EVOO extracts using bioinformatic tools and identified differentially expressed genes enriched in mitochondrial pathways. In vitro validation showed increased mitochondrial mass and DNA driven by enhanced biogenesis and fusion events, accompanied by higher mitochondrial respiration and ATP production. The resulting increase in reactive oxygen species (ROS) triggered a cellular response involving AMPK, NRF2, and antioxidant genes, along with PGC-1 alpha, a master regulator of mitochondrial metabolism. To correlate the biological effects with the components of the secoiridoid-enriched EVOO extracts, we focused on Oleacein (OL) and Oleocanthal (OC). Molecular docking and dynamics simulations predicted both compounds bind to peroxisome proliferator-activated receptor gamma (PPAR gamma) as partial agonists, with OL exhibiting stronger affinity. Treatments with isolated OL and OC mostly replicated the results of the whole extracts. Mechanistically, we provided evidence of the crucial role played by PPAR gamma as the effects on the pathways analyzed were reduced by either blocking the receptor with an irreversible inhibitor and silencing the PPARG gene with specific siRNAs. This study reveals the AMPK-PGC-1 alpha-PPAR gamma axis as a key regulator of OL and OC's effects on mitochondrial function and antioxidant response, supporting their potential as nutraceuticals for health promotion and opening avenues for developing novel PPAR gamma modulators to complement existing therapeutic strategies.

Product ID:

145894

Handle IRIS:

11562/1162594

Last Modified:

May 20, 2025

Bibliographic citation:

Leo, Manuela; Mancini, Caterina; Lori, Giulia; Delre, Pietro; Ferraris, Irene; Lucchini, Filippo; Molinario, Annamaria; Leri, Manuela; Castellaneta, Andrea; Losito, Ilario; Cataldi, Tommaso; Rossato, Marzia; Colantuoni, Vittorio; Taddei, Maria Letizia; Lavecchia, Antonio; Sabatino, Lina, Secoiridoid-enriched extra virgin olive oil extracts enhance mitochondrial activity and antioxidant response in colorectal cancer cells: The role of Oleacein and Oleocanthal in PPARγ interaction «Free Radical Biology and Medicine» , vol. 235 , 2025 , pp. 56-72

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