Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol.
Aberrant DNA methylation is a frequent epigenetic alteration in cancer cells that has emerged as a pivotal mechanism for tumorigenesis. Accordingly, novel therapies targeting the epigenome are being explored with the aim to restore normal DNA methylation patterns on oncogenes and tumor suppressor ge...
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doaj-4c8734d40cec46aba8550efba9e6393e2020-11-25T02:23:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01116e015786610.1371/journal.pone.0157866Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol.Rubiceli Medina-AguilarCarlos Pérez-PlasenciaLaurence A MarchatPatricio GariglioJaime García MenaSergio Rodríguez CuevasErika Ruíz-GarcíaHoracio Astudillo-de la VegaJennifer Hernández JuárezAli Flores-PérezCésar López-CamarilloAberrant DNA methylation is a frequent epigenetic alteration in cancer cells that has emerged as a pivotal mechanism for tumorigenesis. Accordingly, novel therapies targeting the epigenome are being explored with the aim to restore normal DNA methylation patterns on oncogenes and tumor suppressor genes. A limited number of studies indicate that dietary compound resveratrol modulates DNA methylation of several cancer-related genes; however a complete view of changes in methylome by resveratrol has not been reported yet. In this study we performed a genome-wide survey of DNA methylation signatures in triple negative breast cancer cells exposed to resveratrol. Our data showed that resveratrol treatment for 24 h and 48 h decreased gene promoter hypermethylation and increased DNA hypomethylation. Of 2476 hypermethylated genes in control cells, 1,459 and 1,547 were differentially hypomethylated after 24 h and 48 h, respectively. Remarkably, resveratrol did not induce widespread non-specific DNA hyper- or hypomethylation as changes in methylation were found in only 12.5% of 27,728 CpG loci. Moreover, resveratrol restores the hypomethylated and hypermethylated status of key tumor suppressor genes and oncogenes, respectively. Importantly, the integrative analysis of methylome and transcriptome profiles in response to resveratrol showed that methylation alterations were concordant with changes in mRNA expression. Our findings reveal for the first time the impact of resveratrol on the methylome of breast cancer cells and identify novel potential targets for epigenetic therapy. We propose that resveratrol may be considered as a dietary epidrug as it may exert its anti-tumor activities by modifying the methylation status of cancer -related genes which deserves further in vivo characterization.http://europepmc.org/articles/PMC4927060?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rubiceli Medina-Aguilar Carlos Pérez-Plasencia Laurence A Marchat Patricio Gariglio Jaime García Mena Sergio Rodríguez Cuevas Erika Ruíz-García Horacio Astudillo-de la Vega Jennifer Hernández Juárez Ali Flores-Pérez César López-Camarillo |
spellingShingle |
Rubiceli Medina-Aguilar Carlos Pérez-Plasencia Laurence A Marchat Patricio Gariglio Jaime García Mena Sergio Rodríguez Cuevas Erika Ruíz-García Horacio Astudillo-de la Vega Jennifer Hernández Juárez Ali Flores-Pérez César López-Camarillo Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol. PLoS ONE |
author_facet |
Rubiceli Medina-Aguilar Carlos Pérez-Plasencia Laurence A Marchat Patricio Gariglio Jaime García Mena Sergio Rodríguez Cuevas Erika Ruíz-García Horacio Astudillo-de la Vega Jennifer Hernández Juárez Ali Flores-Pérez César López-Camarillo |
author_sort |
Rubiceli Medina-Aguilar |
title |
Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol. |
title_short |
Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol. |
title_full |
Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol. |
title_fullStr |
Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol. |
title_full_unstemmed |
Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol. |
title_sort |
methylation landscape of human breast cancer cells in response to dietary compound resveratrol. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
Aberrant DNA methylation is a frequent epigenetic alteration in cancer cells that has emerged as a pivotal mechanism for tumorigenesis. Accordingly, novel therapies targeting the epigenome are being explored with the aim to restore normal DNA methylation patterns on oncogenes and tumor suppressor genes. A limited number of studies indicate that dietary compound resveratrol modulates DNA methylation of several cancer-related genes; however a complete view of changes in methylome by resveratrol has not been reported yet. In this study we performed a genome-wide survey of DNA methylation signatures in triple negative breast cancer cells exposed to resveratrol. Our data showed that resveratrol treatment for 24 h and 48 h decreased gene promoter hypermethylation and increased DNA hypomethylation. Of 2476 hypermethylated genes in control cells, 1,459 and 1,547 were differentially hypomethylated after 24 h and 48 h, respectively. Remarkably, resveratrol did not induce widespread non-specific DNA hyper- or hypomethylation as changes in methylation were found in only 12.5% of 27,728 CpG loci. Moreover, resveratrol restores the hypomethylated and hypermethylated status of key tumor suppressor genes and oncogenes, respectively. Importantly, the integrative analysis of methylome and transcriptome profiles in response to resveratrol showed that methylation alterations were concordant with changes in mRNA expression. Our findings reveal for the first time the impact of resveratrol on the methylome of breast cancer cells and identify novel potential targets for epigenetic therapy. We propose that resveratrol may be considered as a dietary epidrug as it may exert its anti-tumor activities by modifying the methylation status of cancer -related genes which deserves further in vivo characterization. |
url |
http://europepmc.org/articles/PMC4927060?pdf=render |
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