Epigenetic Effects of Resveratrol on Oncogenic Signaling in Breast Cancer

The crosstalk between oncogenic signaling pathways plays a crucial role in driving cancer development. We previously demonstrated that dietary polyphenols, specifically resveratrol (RSV) and other stilbenoids, epigenetically target oncogenes for silencing via DNA hypermethylation in breast cancer. I...

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Bibliographic Details
Published in:Nutrients 2024-02, Vol.16 (5), p.699
Main Authors: Kurzava Kendall, Lucinda, Ma, Yuexi, Yang, Tony, Lubecka, Katarzyna, Stefanska, Barbara
Format: Article
Language:English
Subjects:
Adjuvant treatment
Analysis
Antibodies
Apoptosis
Autophagy
Breast cancer
Cancer
Cell growth
Cellular signal transduction
Chromatin
DNA methylation
Drug resistance
Epigenetic inheritance
Epigenetics
Gene expression
Genes
Genetic aspects
Genomes
Medical prognosis
Metastasis
Methylation
Oncology, Experimental
Penicillin
Polyphenols
Prevention
Prostate cancer
Resveratrol
Scientific equipment and supplies industry
Signal transduction
Stem cells
Transcription factors
Tumors
Viral antibodies
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Summary:The crosstalk between oncogenic signaling pathways plays a crucial role in driving cancer development. We previously demonstrated that dietary polyphenols, specifically resveratrol (RSV) and other stilbenoids, epigenetically target oncogenes for silencing via DNA hypermethylation in breast cancer. In the present study, we identify signal transduction regulators among RSV-hypermethylated targets and investigate the functional role of RSV-mediated DNA hypermethylation in the regulation of Hedgehog and Wnt signaling. Non-invasive ER-positive MCF-7 and highly invasive triple-negative MCF10CA1a human breast cancer cell lines were used as experimental models. Upon 9-day exposure to 15 µM RSV, pyrosequencing and qRT-PCR were performed to assess DNA methylation and expression of and , which are upstream regulators of the Hedgehog and Wnt pathways, respectively. Our results showed that RSV led to a DNA methylation increase within and enhancers, which was accompanied by decreases in gene expression. Consistently, we observed the downregulation of genes downstream of the Hedgehog and Wnt signaling, including common targets shared by both pathways, and . Further analysis using chromatin immunoprecipitation identified increased H3K27 trimethylation and decreased H3K9 and H3K27 acetylation, along with abolishing OCT1 transcription factor binding. Those changes indicate a transcriptionally silent chromatin state at and enhancers. The inhibition of the Wnt signal transduction was confirmed using a phospho-antibody array that demonstrated suppression of positive and stimulation of negative Wnt regulators. In conclusion, our results provide scientific evidence for dietary polyphenols as epigenetics-modulating agents that act to re-methylate and silence oncogenes, reducing the oncogenic signal transduction. Targeting such an action could be an effective strategy in breast cancer prevention and/or adjuvant therapy.
ISSN:2072-6643
2072-6643
DOI:10.3390/nu16050699