Methylation landscape of human breast cancer cells in response to dietary compound resveratrol

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

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Abstract

© 2016 Medina-Aguilar et al. 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. 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.
Original languageAmerican English
JournalPLoS ONE
DOIs
StatePublished - 1 Jun 2016

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Methylation
resveratrol
methylation
breast neoplasms
Cells
Breast Neoplasms
Genes
DNA methylation
DNA Methylation
Tumors
tumor suppressor genes
Neoplasm Genes
oncogenes
Tumor Suppressor Genes
Oncogenes
Epigenomics
epigenetics
neoplasms
genes
Triple Negative Breast Neoplasms

Cite this

Medina-Aguilar, R., Pérez-Plasencia, C., Marchat, L. A., Gariglio, P., García Mena, J., Rodríguez Cuevas, S., ... López-Camarillo, C. (2016). Methylation landscape of human breast cancer cells in response to dietary compound resveratrol. PLoS ONE. https://doi.org/10.1371/journal.pone.0157866
Medina-Aguilar, Rubiceli ; Pérez-Plasencia, Carlos ; Marchat, Laurence A. ; Gariglio, Patricio ; García Mena, Jaime ; Rodríguez Cuevas, Sergio ; Ruíz-García, Erika ; Astudillo-De La Vega, Horacio ; Hernández Juárez, Jennifer ; Flores-Pérez, Ali ; López-Camarillo, César. / Methylation landscape of human breast cancer cells in response to dietary compound resveratrol. In: PLoS ONE. 2016.
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Medina-Aguilar, R, Pérez-Plasencia, C, Marchat, LA, Gariglio, P, García Mena, J, Rodríguez Cuevas, S, Ruíz-García, E, Astudillo-De La Vega, H, Hernández Juárez, J, Flores-Pérez, A & López-Camarillo, C 2016, 'Methylation landscape of human breast cancer cells in response to dietary compound resveratrol', PLoS ONE. https://doi.org/10.1371/journal.pone.0157866

Methylation landscape of human breast cancer cells in response to dietary compound resveratrol. / Medina-Aguilar, Rubiceli; Pérez-Plasencia, Carlos; Marchat, Laurence A.; Gariglio, Patricio; García Mena, Jaime; Rodríguez Cuevas, Sergio; Ruíz-García, Erika; Astudillo-De La Vega, Horacio; Hernández Juárez, Jennifer; Flores-Pérez, Ali; López-Camarillo, César.

In: PLoS ONE, 01.06.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Methylation landscape of human breast cancer cells in response to dietary compound resveratrol

AU - Medina-Aguilar, Rubiceli

AU - Pérez-Plasencia, Carlos

AU - Marchat, Laurence A.

AU - Gariglio, Patricio

AU - García Mena, Jaime

AU - Rodríguez Cuevas, Sergio

AU - Ruíz-García, Erika

AU - Astudillo-De La Vega, Horacio

AU - Hernández Juárez, Jennifer

AU - Flores-Pérez, Ali

AU - López-Camarillo, César

PY - 2016/6/1

Y1 - 2016/6/1

N2 - © 2016 Medina-Aguilar et al. 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. 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.

AB - © 2016 Medina-Aguilar et al. 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. 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.

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Medina-Aguilar R, Pérez-Plasencia C, Marchat LA, Gariglio P, García Mena J, Rodríguez Cuevas S et al. Methylation landscape of human breast cancer cells in response to dietary compound resveratrol. PLoS ONE. 2016 Jun 1. https://doi.org/10.1371/journal.pone.0157866