Novel inhibitory effect of Omega-3 fatty acids regulating pancreatic cancer progression.

Autor:	Garay MI; Instituto de Investigaciones en Ciencias de la Salud, INICSA (CONICET - FCM UNC), 5016 Córdoba, Argentina.; Instituto de Biología Celular y Cátedra de Biología Celular, Histología y Embriología, FCM-UNC, 5016 Córdoba, Argentina., Mazo T; Instituto de Investigaciones en Ciencias de la Salud, INICSA (CONICET - FCM UNC), 5016 Córdoba, Argentina.; Instituto de Biología Celular y Cátedra de Biología Celular, Histología y Embriología, FCM-UNC, 5016 Córdoba, Argentina., Ferrero V; Instituto de Investigaciones en Ciencias de la Salud, INICSA (CONICET - FCM UNC), 5016 Córdoba, Argentina.; Instituto de Biología Celular y Cátedra de Biología Celular, Histología y Embriología, FCM-UNC, 5016 Córdoba, Argentina., Barotto NN; Instituto de Biología Celular y Cátedra de Biología Celular, Histología y Embriología, FCM-UNC, 5016 Córdoba, Argentina., Lagares C; Instituto de Investigaciones en Ciencias de la Salud, INICSA (CONICET - FCM UNC), 5016 Córdoba, Argentina., Granton MF; Instituto de Biología Celular y Cátedra de Biología Celular, Histología y Embriología, FCM-UNC, 5016 Córdoba, Argentina., Moreira-Espinoza MJ; Instituto de Biología Celular y Cátedra de Biología Celular, Histología y Embriología, FCM-UNC, 5016 Córdoba, Argentina., Cremonezzi DC; Departamento de Patología, Hospital Nacional de Clínicas, FCM-UNC, 5000 Córdoba, Argentina., Comba A; Department of Pathology, Division Neuropathology, Heersink School of Medicine, University of Alabama at Birmingham, AL, 35294, USA., Brunotto MN; Instituto de Investigaciones en Ciencias de la Salud, INICSA (CONICET - FCM UNC), 5016 Córdoba, Argentina.; Departamento de Biología Bucal, Facultad de Odontología, UNC, 5016 Córdoba, Argentina., Tolosa EJ; Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN 55905, USA., Fernandez-Zapico ME; Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN 55905, USA., Pasqualini ME; Instituto de Investigaciones en Ciencias de la Salud, INICSA (CONICET - FCM UNC), 5016 Córdoba, Argentina.; Instituto de Biología Celular y Cátedra de Biología Celular, Histología y Embriología, FCM-UNC, 5016 Córdoba, Argentina.
Jazyk:	angličtina
Zdroj:	Carcinogenesis [Carcinogenesis] 2025 Jan 01. Date of Electronic Publication: 2025 Jan 01.
DOI:	10.1093/carcin/bgae081
Abstrakt:	Pancreatic cancer is a devastating malignancy in great need of new and more effective treatment approaches. In recent years, studies have indicated that nutritional interventions, particularly nutraceuticals, may provide novel avenues to modulate cancer progression. Here, our study characterizes the impact of ω-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as a nutraceutical intervention in pancreatic cancer using a genetically engineered mouse model driven by KrasG12D and Trp53R172H. This model closely resembles human pancreatic carcinogenesis, offering a disease relevant platform for translational research. Our findings showed that ω-3 PUFAs intervention (using a diet supplemented with 6% cod liver oil) significantly reduced tumor volume as well as lung and liver metastasis and a trend towards improved survival rate compared to control treated mice. This antitumoral effect was accompanied by distinct changes in tumor membrane fatty acid profile and eicosanoids release. Further, the EPA and DHA intervention also reduced malignant histological parameters and induced apoptosis without affecting cell proliferation. Of note is the significant reduction in tumor fibrosis that was associated with decreased levels of Sonic Hedgehog (SHH), a major ligand controlling this cellular compartment in pancreatic cancer. All together our results demonstrate the impact of EPA and DHA as antitumor regulators in pancreatic cancer, suggesting potential for ω-3 PUFAs as a possible antitumoral dietary intervention. This research opens new avenues for integrating nutraceutical strategies in pancreatic cancer management. (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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