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Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring
Diets rich in omega-3 fatty acids (FA) have been associated with lowered risks of developing certain types of cancers. We earlier reported that in transgenic mice prone to develop breast cancer (BCa), a diet supplemented with canola oil, rich in omega-3-rich FA (as opposed to an omega-6-rich diet co...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222782/ https://www.ncbi.nlm.nih.gov/pubmed/34179012 http://dx.doi.org/10.3389/fcell.2021.682593 |
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author | Abbas, Ata Witte, Theodore Patterson, William L. Fahrmann, Johannes F. Guo, Kai Hur, Junguk Hardman, W. Elaine Georgel, Philippe T. |
author_facet | Abbas, Ata Witte, Theodore Patterson, William L. Fahrmann, Johannes F. Guo, Kai Hur, Junguk Hardman, W. Elaine Georgel, Philippe T. |
author_sort | Abbas, Ata |
collection | PubMed |
description | Diets rich in omega-3 fatty acids (FA) have been associated with lowered risks of developing certain types of cancers. We earlier reported that in transgenic mice prone to develop breast cancer (BCa), a diet supplemented with canola oil, rich in omega-3-rich FA (as opposed to an omega-6-rich diet containing corn oil), reduced the risk of developing BCa, and also significantly reduced the incidence of BCa in F1 offspring. To investigate the underlying mechanisms of the cancer protective effect of canola oil in the F1 generation, we designed and performed the present study with the same diets using BALB/c mice to remove any possible effect of the transgene. First, we observed epigenetic changes at the genome-wide scale in F1 offspring of mothers fed diets containing omega-3 FAs, including a significant increase in acetylation of H3K18 histone mark and a decrease in H3K4me2 mark on nucleosomes around transcription start sites. These epigenetic modifications contribute to differential gene expressions associated with various pathways and molecular mechanisms involved in preventing cancer development, including p53 pathway, G2M checkpoint, DNA repair, inflammatory response, and apoptosis. When offspring mice were exposed to 7,12-Dimethylbenz(a)anthracene (DMBA), the group of mice exposed to a canola oil (with omega 3 FAs)-rich maternal diet showed delayed mortality, increased survival, reduced lateral tumor growth, and smaller tumor size. Remarkably, various genes, including BRCA genes, appear to be epigenetically re-programmed to poise genes to be ready for a rapid transcriptional activation due to the canola oil-rich maternal diet. This ability to respond rapidly due to epigenetic potentiation appeared to contribute to and promote protection against breast cancer after carcinogen exposure. |
format | Online Article Text |
id | pubmed-8222782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82227822021-06-25 Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring Abbas, Ata Witte, Theodore Patterson, William L. Fahrmann, Johannes F. Guo, Kai Hur, Junguk Hardman, W. Elaine Georgel, Philippe T. Front Cell Dev Biol Cell and Developmental Biology Diets rich in omega-3 fatty acids (FA) have been associated with lowered risks of developing certain types of cancers. We earlier reported that in transgenic mice prone to develop breast cancer (BCa), a diet supplemented with canola oil, rich in omega-3-rich FA (as opposed to an omega-6-rich diet containing corn oil), reduced the risk of developing BCa, and also significantly reduced the incidence of BCa in F1 offspring. To investigate the underlying mechanisms of the cancer protective effect of canola oil in the F1 generation, we designed and performed the present study with the same diets using BALB/c mice to remove any possible effect of the transgene. First, we observed epigenetic changes at the genome-wide scale in F1 offspring of mothers fed diets containing omega-3 FAs, including a significant increase in acetylation of H3K18 histone mark and a decrease in H3K4me2 mark on nucleosomes around transcription start sites. These epigenetic modifications contribute to differential gene expressions associated with various pathways and molecular mechanisms involved in preventing cancer development, including p53 pathway, G2M checkpoint, DNA repair, inflammatory response, and apoptosis. When offspring mice were exposed to 7,12-Dimethylbenz(a)anthracene (DMBA), the group of mice exposed to a canola oil (with omega 3 FAs)-rich maternal diet showed delayed mortality, increased survival, reduced lateral tumor growth, and smaller tumor size. Remarkably, various genes, including BRCA genes, appear to be epigenetically re-programmed to poise genes to be ready for a rapid transcriptional activation due to the canola oil-rich maternal diet. This ability to respond rapidly due to epigenetic potentiation appeared to contribute to and promote protection against breast cancer after carcinogen exposure. Frontiers Media S.A. 2021-06-10 /pmc/articles/PMC8222782/ /pubmed/34179012 http://dx.doi.org/10.3389/fcell.2021.682593 Text en Copyright © 2021 Abbas, Witte, Patterson, Fahrmann, Guo, Hur, Hardman and Georgel. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Abbas, Ata Witte, Theodore Patterson, William L. Fahrmann, Johannes F. Guo, Kai Hur, Junguk Hardman, W. Elaine Georgel, Philippe T. Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring |
title | Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring |
title_full | Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring |
title_fullStr | Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring |
title_full_unstemmed | Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring |
title_short | Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring |
title_sort | epigenetic reprogramming mediated by maternal diet rich in omega-3 fatty acids protects from breast cancer development in f1 offspring |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222782/ https://www.ncbi.nlm.nih.gov/pubmed/34179012 http://dx.doi.org/10.3389/fcell.2021.682593 |
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