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, M., Rinzo, P., Mattioli, R., Moschella, F., Cristina Quattrini, M., Pietraforte, D., Donati, S., Rossi, S., Laterza, I., Maroccia, Z., Leoni, O., Macchia, D., Spada, M., Tomasoni6, S., Verin, R., Panebianco, C., Pazienza, V., Mosca, L., Fabbri, A., Bracci, L.. - (2025). (ACC - Alleanza contro il cancro 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.
