Despite advancements in early detection and treatment, colorectal cancer (CRC) rates and mortality remain high, underscoring the need for novel preventive and therapeutic strategies. Increasing evidence suggests that extra-virgin olive oil (EVOO) bioactive polyphenols have strong biological effects in various disease models (Di Pietro, M. Front Pharmacol 2022) including antitumor properties. An innovative, eco-friendly method for isolating EVOO polyphenols using Natural Deep Eutectic Solvents (NaDES) has been recently developed (Francioso, A. Molecules 2020). The present study aims to evaluate the antitumor effects of EVOO polyphenols extracted by NaDES (Poly-NaDES) in a highly aggressive CRC mouse model. At first, the direct antitumor effects of Poly-NaDES were evaluated by MTT assay on a panel of neoplastic and non-neoplastic intestinal epithelial cell lines. Electron Paramagnetic Resonance analysis demonstrated that Poly-NaDES counteracted the ROS production and the consequent phosphorylation of the histone H2AX induced by E.coli CNF1, a bacterial toxin with pro-carcinogenic effects (Tozzi, M. J Exp Clin Cancer Res 2025), on intestinal cells, suggesting a protective effect against CNF1-induced DNA damage. In vivo, we used a well-established murine model of colorectal carcinogenesis induced by azoxymethane (AOM) and dextran sodium sulphate (DSS). To accelerate tumor development and increase malignancy, mice received three intrarectal instillations of CNF1. This treatment resulted in the development of highly aggressive adenomas and adenocarcinomas in 100% of mice, as confirmed by histopathological assessment of colon sections. Interestingly, the daily Poly-NaDES administration (5mg/kg/die) in the drinking water for 60 days, reduced inflammatory infiltrates and revealed the presence of colorectal adenomas with low mitotic index and low expression of 53BP1, a marker of DNA damage, as assessed by H&E staining of colon tissue. Overall, our findings indicate that Poly-NaDES may counteract CNF1-induced pro-tumor effects by reducing oxidative DNA damage, with potential implications for colorectal cancer prevention and treatment.
Evaluation of the antitumor effects of extra-virgin olive oil phenolic compounds extracted by a novel “green” chemistry approach: focus on oxidative genotoxic stress and inflammation / Tozzi, Michela; Rinzo, Paola; Mattioli, Roberto; Moschella, Federica; Cristina Quattrini, Maria; Pietraforte, Donatella; Laterza, Ilenia; Maroccia, Zaira; Leoni, Omar; Macchia, Daniele; Spada, Massimo; Tomasoni, Sofia; Verin, Ranieri; Mosca, Luciana; Panebianco, Concetta; Pazienza, Valerio; Fabbri, Alessia; Bracci, Laura. - (2025). (Intervento presentato al convegno SIICA- Società Italiana Immunologia, Immunologia Clinica e Allergologia tenutosi a Perugia).
Evaluation of the antitumor effects of extra-virgin olive oil phenolic compounds extracted by a novel “green” chemistry approach: focus on oxidative genotoxic stress and inflammation
Michela Tozzi;Paola Rinzo;Roberto Mattioli;Ilenia Laterza;Luciana Mosca;
2025
Abstract
Despite advancements in early detection and treatment, colorectal cancer (CRC) rates and mortality remain high, underscoring the need for novel preventive and therapeutic strategies. Increasing evidence suggests that extra-virgin olive oil (EVOO) bioactive polyphenols have strong biological effects in various disease models (Di Pietro, M. Front Pharmacol 2022) including antitumor properties. An innovative, eco-friendly method for isolating EVOO polyphenols using Natural Deep Eutectic Solvents (NaDES) has been recently developed (Francioso, A. Molecules 2020). The present study aims to evaluate the antitumor effects of EVOO polyphenols extracted by NaDES (Poly-NaDES) in a highly aggressive CRC mouse model. At first, the direct antitumor effects of Poly-NaDES were evaluated by MTT assay on a panel of neoplastic and non-neoplastic intestinal epithelial cell lines. Electron Paramagnetic Resonance analysis demonstrated that Poly-NaDES counteracted the ROS production and the consequent phosphorylation of the histone H2AX induced by E.coli CNF1, a bacterial toxin with pro-carcinogenic effects (Tozzi, M. J Exp Clin Cancer Res 2025), on intestinal cells, suggesting a protective effect against CNF1-induced DNA damage. In vivo, we used a well-established murine model of colorectal carcinogenesis induced by azoxymethane (AOM) and dextran sodium sulphate (DSS). To accelerate tumor development and increase malignancy, mice received three intrarectal instillations of CNF1. This treatment resulted in the development of highly aggressive adenomas and adenocarcinomas in 100% of mice, as confirmed by histopathological assessment of colon sections. Interestingly, the daily Poly-NaDES administration (5mg/kg/die) in the drinking water for 60 days, reduced inflammatory infiltrates and revealed the presence of colorectal adenomas with low mitotic index and low expression of 53BP1, a marker of DNA damage, as assessed by H&E staining of colon tissue. Overall, our findings indicate that Poly-NaDES may counteract CNF1-induced pro-tumor effects by reducing oxidative DNA damage, with potential implications for colorectal cancer prevention and treatment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
