Despite advancements in early detection and treatment, colorectal cancer (CRC) remains a major cause of cancer-related morbidity and mortality worldwide, underscoring the urgent need for novel preventive and therapeutic strategies. Emerging evidence highlights the potent biological effects of extra-virgin olive oil (EVOO) polyphenols, including their anti-inflammatory and anti-tumor properties (1). Recently, an eco-compatible extraction method using Natural Deep Eutectic Solvents (NaDES) has been developed to isolate these bioactive compounds from EVOO (Poly-NaDES) (2). The present study aims to investigate the anti-tumor effects of Poly-NaDES and the underlying mechanisms in vitro and in a highly aggressive CRC mouse model, where CNF1 toxin from Escherichia coli is added to the AOM/DSS carcinogenesis model to accelerate tumor development. In vitro, we demonstrated that Poly-NaDES significantly reduced CNF1-induced reactive oxidizing species production in intestinal epithelial cells (IEC-6) and immune cells (THP1) and, consequently, attenuated CNF1-induced phosphorylation of histone H2AX, a marker of DNA-damage response. However, Poly-NaDES did not impair CNF1-induced chromosomal aberrations nor 53BP1 foci formation, suggesting that these compounds could not directly hinder CNF1-induced genotoxicity. Nevertheless, Poly-NaDES completely abrogated the pro-inflammatory cytokine release induced by CNF1 in THP1 cells and preserved the epithelial barrier integrity by counteracting CNF1-induced permeability loss in Caco-2 monolayers. In vivo, daily supplementation with Poly-NaDES for 60 days reduced inflammatory infiltrates in colonic tissue and delayed tumor development. Poly-NaDES use increased gut microbial diversity and richness, though not statistically significant. In conclusion, Poly-NaDES appear to counteract CNF1-driven tumorigenesis through anti-oxidant and anti-inflammatory effects, thereby preserving intestinal homeostasis.
Extra-virgin olive oil polyphenols extracted by a “green chemistry” approach hold promising antitumor effects against colorectal cancer: implications for cancer chemoprevention / Tozzi, Michela; Rinzo, Paola; Mattioli, Roberto; Moschella, Federica; Cristina Quattrini, Maria; Pietraforte, Donatella; Donati, Simona; Rossi, Stefania; Laterza, Ilenia; Maroccia, Zaira; Leoni, Omar; Macchia, Daniele; Spada, Massimo; Tomasoni6, Sofia; Verin, Ranieri; Panebianco, Concetta; Pazienza, Valerio; Mosca, Luciana; Fabbri, Alessia; Bracci, Laura. - (2025). (Intervento presentato al convegno ACC - Alleanza contro il cancro tenutosi a Verona).
Extra-virgin olive oil polyphenols extracted by a “green chemistry” approach hold promising antitumor effects against colorectal cancer: implications for cancer chemoprevention
Michela Tozzi;Paola Rinzo;Roberto Mattioli;Ilenia Laterza;Luciana Mosca;
2025
Abstract
Despite advancements in early detection and treatment, colorectal cancer (CRC) remains a major cause of cancer-related morbidity and mortality worldwide, underscoring the urgent need for novel preventive and therapeutic strategies. Emerging evidence highlights the potent biological effects of extra-virgin olive oil (EVOO) polyphenols, including their anti-inflammatory and anti-tumor properties (1). Recently, an eco-compatible extraction method using Natural Deep Eutectic Solvents (NaDES) has been developed to isolate these bioactive compounds from EVOO (Poly-NaDES) (2). The present study aims to investigate the anti-tumor effects of Poly-NaDES and the underlying mechanisms in vitro and in a highly aggressive CRC mouse model, where CNF1 toxin from Escherichia coli is added to the AOM/DSS carcinogenesis model to accelerate tumor development. In vitro, we demonstrated that Poly-NaDES significantly reduced CNF1-induced reactive oxidizing species production in intestinal epithelial cells (IEC-6) and immune cells (THP1) and, consequently, attenuated CNF1-induced phosphorylation of histone H2AX, a marker of DNA-damage response. However, Poly-NaDES did not impair CNF1-induced chromosomal aberrations nor 53BP1 foci formation, suggesting that these compounds could not directly hinder CNF1-induced genotoxicity. Nevertheless, Poly-NaDES completely abrogated the pro-inflammatory cytokine release induced by CNF1 in THP1 cells and preserved the epithelial barrier integrity by counteracting CNF1-induced permeability loss in Caco-2 monolayers. In vivo, daily supplementation with Poly-NaDES for 60 days reduced inflammatory infiltrates in colonic tissue and delayed tumor development. Poly-NaDES use increased gut microbial diversity and richness, though not statistically significant. In conclusion, Poly-NaDES appear to counteract CNF1-driven tumorigenesis through anti-oxidant and anti-inflammatory effects, thereby preserving intestinal homeostasis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
