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Prevention of diabetes-promoted colorectal cancer by (n-3) polyunsaturated fatty acids and (n-3) PUFA mimetic

The global obesity / diabetes epidemic has resulted in robust increase in the incidence of colorectal cancer (CRC). Epidemiological, animal and human studies have indicated efficacy of (n-3) PUFA in chemoprevention of sporadic and genetic-driven CRC. However, diabetes-promoted CRC presents a treatme...

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Autores principales: Algamas-Dimantov, Anna, Yehuda-Shnaidman, Einav, Hertz, Rachel, Peri, Irena, Bar-Tana, Jacob, Schwartz, Betty
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259442/
https://www.ncbi.nlm.nih.gov/pubmed/25375205
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author Algamas-Dimantov, Anna
Yehuda-Shnaidman, Einav
Hertz, Rachel
Peri, Irena
Bar-Tana, Jacob
Schwartz, Betty
author_facet Algamas-Dimantov, Anna
Yehuda-Shnaidman, Einav
Hertz, Rachel
Peri, Irena
Bar-Tana, Jacob
Schwartz, Betty
author_sort Algamas-Dimantov, Anna
collection PubMed
description The global obesity / diabetes epidemic has resulted in robust increase in the incidence of colorectal cancer (CRC). Epidemiological, animal and human studies have indicated efficacy of (n-3) PUFA in chemoprevention of sporadic and genetic-driven CRC. However, diabetes-promoted CRC presents a treatment challenge that surpasses that of sporadic CRC. This report analyzes the efficacy of (n-3) PUFA generated by the fat-1 transgene that encodes an (n-6) to (n-3) PUFA desaturase, and of synthetic (n-3) PUFA mimetic (MEDICA analog), to suppress CRC development in carcinogen-induced diabetes-promoted animal model. Carcinogen-induced CRC is shown here to be promoted by the diabetes context, in terms of increased aberrant crypt foci (ACF) load, cell proliferation and epithelial dedifferentiation, being accompanied by increase in the expression of HNF4α, β-catenin, and β-catenin-responsive genes. Incorporating the fat-1 transgene in the diabetes context, or oral MEDICA treatment, resulted in ameliorating the diabetic phenotype and in abrogating CRC, with decrease in ACF load, cell proliferation and the expression of HNF-4α, β-catenin, and β-catenin-responsive genes. The specificity of (n-3) PUFA in abrogating CRC development, as contrasted with enhancing CRC by (n-6) PUFA, was similarly verified in CRC cell lines. These findings may indicate prospective therapeutic potential of (n-3) PUFA or MEDICA in the management of CRC, in particular diabetes-promoted CRC.
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spelling pubmed-42594422014-12-10 Prevention of diabetes-promoted colorectal cancer by (n-3) polyunsaturated fatty acids and (n-3) PUFA mimetic Algamas-Dimantov, Anna Yehuda-Shnaidman, Einav Hertz, Rachel Peri, Irena Bar-Tana, Jacob Schwartz, Betty Oncotarget Research Paper The global obesity / diabetes epidemic has resulted in robust increase in the incidence of colorectal cancer (CRC). Epidemiological, animal and human studies have indicated efficacy of (n-3) PUFA in chemoprevention of sporadic and genetic-driven CRC. However, diabetes-promoted CRC presents a treatment challenge that surpasses that of sporadic CRC. This report analyzes the efficacy of (n-3) PUFA generated by the fat-1 transgene that encodes an (n-6) to (n-3) PUFA desaturase, and of synthetic (n-3) PUFA mimetic (MEDICA analog), to suppress CRC development in carcinogen-induced diabetes-promoted animal model. Carcinogen-induced CRC is shown here to be promoted by the diabetes context, in terms of increased aberrant crypt foci (ACF) load, cell proliferation and epithelial dedifferentiation, being accompanied by increase in the expression of HNF4α, β-catenin, and β-catenin-responsive genes. Incorporating the fat-1 transgene in the diabetes context, or oral MEDICA treatment, resulted in ameliorating the diabetic phenotype and in abrogating CRC, with decrease in ACF load, cell proliferation and the expression of HNF-4α, β-catenin, and β-catenin-responsive genes. The specificity of (n-3) PUFA in abrogating CRC development, as contrasted with enhancing CRC by (n-6) PUFA, was similarly verified in CRC cell lines. These findings may indicate prospective therapeutic potential of (n-3) PUFA or MEDICA in the management of CRC, in particular diabetes-promoted CRC. Impact Journals LLC 2014-09-08 /pmc/articles/PMC4259442/ /pubmed/25375205 Text en Copyright: © 2014 Algamas-Dimantov et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Algamas-Dimantov, Anna
Yehuda-Shnaidman, Einav
Hertz, Rachel
Peri, Irena
Bar-Tana, Jacob
Schwartz, Betty
Prevention of diabetes-promoted colorectal cancer by (n-3) polyunsaturated fatty acids and (n-3) PUFA mimetic
title Prevention of diabetes-promoted colorectal cancer by (n-3) polyunsaturated fatty acids and (n-3) PUFA mimetic
title_full Prevention of diabetes-promoted colorectal cancer by (n-3) polyunsaturated fatty acids and (n-3) PUFA mimetic
title_fullStr Prevention of diabetes-promoted colorectal cancer by (n-3) polyunsaturated fatty acids and (n-3) PUFA mimetic
title_full_unstemmed Prevention of diabetes-promoted colorectal cancer by (n-3) polyunsaturated fatty acids and (n-3) PUFA mimetic
title_short Prevention of diabetes-promoted colorectal cancer by (n-3) polyunsaturated fatty acids and (n-3) PUFA mimetic
title_sort prevention of diabetes-promoted colorectal cancer by (n-3) polyunsaturated fatty acids and (n-3) pufa mimetic
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259442/
https://www.ncbi.nlm.nih.gov/pubmed/25375205
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