ArticleCarcinogenesis2016
Stilbenoids remodel the DNA methylation patterns in breast cancer cells and inhibit oncogenic NOTCH signaling through epigenetic regulation of MAML2 transcriptional activity.
Article in Carcinogenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 101 citations in OpenAlex.
- Effects of the MAML2 genetic variants in glioma susceptibility and prognosis.Bioscience reports · 2019Trial
- AMPK-Dependent Epigenetic Regulation of Metabolism Mediates the Anti-Cancer Action of Pterostilbene in Hepatocellular Carcinoma.Molecular nutrition & food research · 2025Article
- Mediterranean Diet and Agri-Food By-Products: A Possible Sustainable Approach for Breast Cancer Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- Advances in antitumor effects of pterostilbene and its derivatives.Future medicinal chemistry · 2025Review
- Multi-omics and clustering analyses reveal the mechanisms underlying unmet needs for patients with lung adenocarcinoma and identify potential therapeutic targets.Molecular cancer · 2024Article
- Adherence to the Mediterranean Diet and its association with gastric cancer: health benefits from a Planeterranean perspective.Journal of translational medicine · 2024Review
- Comprehensive analysis of DNA methylation gene expression profiles in GEO dataset reveals biomarkers related to malignant transformation of sinonasal inverted papilloma.Discover oncology · 2024Article
- Article
- Targeting Notch signaling pathways with natural bioactive compounds: a promising approach against cancer.Frontiers in pharmacology · 2024Review
- Isorhapontigenin (ISO) inhibits malignant cell transformation, migration, and invasion through MEG3/NEDD9 signaling in Cr(VI)-transformed cells.Toxicology and applied pharmacology · 2023Article
- Gender Differences in Oxidative Stress in Relation to Cancer Susceptibility and Survival.Antioxidants (Basel, Switzerland) · 2023Review
- Lunasin and Its Epigenetic Impact in Cancer Chemoprevention.International journal of molecular sciences · 2023Review
- Pterostilbene in the treatment of inflammatory and oncological diseases.Frontiers in pharmacology · 2023Review
- Inferring cancer common and specific gene networks via multi-layer joint graphical model.Computational and structural biotechnology journal · 2023Article
- Notch signaling pathway: a comprehensive prognostic and gene expression profile analysis in breast cancer.BMC cancer · 2022Article
- DNA hypermethylation ofEpigenetics · 2022Article
- Evidence for Multilevel Chemopreventive Activities of Natural Phenols from Functional Genomic Studies of Curcumin, Resveratrol, Genistein, Quercetin, and Luteolin.International journal of molecular sciences · 2022Review
- DNA Methylome and Transcriptome Study of Triterpenoid CDDO in TPA-Mediated Skin Carcinogenesis Model.The AAPS journal · 2022Article
- Epigenetic aberrations of gene expression in a rat model of hepatocellular carcinoma.Epigenetics · 2022Article
- Molecular Effects of Iodine-Biofortified Lettuce in Human Gastrointestinal Cancer Cells.Nutrients · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
DNA hypomethylation was previously implicated in cancer progression and metastasis. The purpose of this study was to examine whether stilbenoids, resveratrol and pterostilbene thought to exert anticancer effects, target genes with oncogenic function for de novo methylation and silencing, leading to inactivation of related signaling pathways. Following Illumina 450K, genome-wide DNA methylation analysis reveals that stilbenoids alter DNA methylation patterns in breast cancer cells. On average, 75% of differentially methylated genes have increased methylation, and these genes are enriched for oncogenic functions, including NOTCH signaling pathway. MAML2, a coactivator of NOTCH targets, is methylated at the enhancer region and transcriptionally silenced in response to stilbenoids, possibly explaining the downregulation of NOTCH target genes. The increased DNA methylation at MAML2 enhancer coincides with increased occupancy of repressive histone marks and decrease in activating marks. This condensed chromatin structure is associated with binding of DNMT3B and decreased occupancy of OCT1 transcription factor at MAML2 enhancer, suggesting a role of DNMT3B in increasing methylation of MAML2 after stilbenoid treatment. Our results deliver a novel insight into epigenetic regulation of oncogenic signals in cancer and provide support for epigenetic-targeting strategies as an effective anticancer approach.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.