ArticleOncotarget2017
Epigenetic silencing of triple negative breast cancer hallmarks by Withaferin A.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 68 citations in OpenAlex.
- Phytochemical Characterization of Tupistra nutans Inflorescence and its Cytostatic and Anti-Migratory Effect in Breast Cancer Cells.Applied biochemistry and biotechnology · 2026Article
- Combined Effects of Withaferin A and Sodium Butyrate on NF-κB Signaling and Epigenetic Regulation in Breast Cancer Cells.Nutrients · 2026Article
- Mechanisms and potential therapeutic strategies of withaferin A in breast cancer.Pharmacological reports : PR · 2025Review
- Article
- Reflections and perspectives on epigenetically mediated biological control: compromises in cancer and skeletal pathology.Academia biology · 2025Article
- The Therapeutic Effects of Withaferin A against Cancer: Overview and Updates.Current molecular medicine · 2024Review
- Unlocking the epigenetic code: new insights into triple-negative breast cancer.Frontiers in oncology · 2024Review
- Management of triple-negative breast cancer by natural compounds through different mechanistic pathways.Frontiers in genetics · 2024Review
- Phytocompounds targeting epigenetic modulations: an assessment in cancer.Frontiers in pharmacology · 2023Review
- Functional Validation of the Putative Oncogenic Activity ofBiomedicines · 2022Article
- Article
- Review
- Ferroptosis Induction in Multiple Myeloma Cells Triggers DNA Methylation and Histone Modification Changes Associated with Cellular Senescence.International journal of molecular sciences · 2021Article
- Anticancer mechanisms of phytochemical compounds: focusing on epigenetic targets.Environmental science and pollution research international · 2021Review
- Echinacea purpurea (L.) Moench treatment of monocytes promotes tonic interferon signaling, increased innate immunity gene expression and DNA repeat hypermethylated silencing of endogenous retroviral sequences.BMC complementary medicine and therapies · 2021Article
- A Comprehensive Review and Perspective on Anticancer Mechanisms of Withaferin A in Breast Cancer.Cancer prevention research (Philadelphia, Pa.) · 2020Review
- Unraveling the Genomic-Epigenomic Interaction Landscape in Triple Negative and Non-Triple Negative Breast Cancer.Cancers · 2020Article
- Exploring the Regulation Mechanism of Xihuang Pill,Frontiers in pharmacology · 2020Article
- Plasma GBP2 promoter methylation is associated with advanced stages in breast cancer.Genetics and molecular biology · 2020Article
- Epigenetic Regulation and Dietary Control of Triple Negative Breast Cancer.Frontiers in nutrition · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple negative breast cancer (TNBC) is characterized by poor prognosis and a DNA hypomethylation profile. Withaferin A (WA) is a plant derived steroidal lactone which holds promise as a therapeutic agent for treatment of breast cancer (BC). We determined genome-wide DNA methylation changes in weakly-metastatic and aggressive, metastatic BC cell lines, following 72h treatment to a sub-cytotoxic concentration of WA. In contrast to the DNA demethylating agent 5-aza-2'-deoxycytidine (DAC), WA treatment of MDA-MB-231 cells rather tackles an epigenetic cancer network through gene-specific DNA hypermethylation of tumor promoting genes including ADAM metallopeptidase domain 8 (ADAM8), urokinase-type plasminogen activator (PLAU), tumor necrosis factor (ligand) superfamily, member 12 (TNFSF12), and genes related to detoxification (glutathione S-transferase mu 1, GSTM1), or mitochondrial metabolism (malic enzyme 3, ME3). Gene expression and pathway enrichment analysis further reveals epigenetic suppression of multiple cancer hallmarks associated with cell cycle regulation, cell death, cancer cell metabolism, cell motility and metastasis. Remarkably, DNA hypermethylation of corresponding CpG sites in PLAU, ADAM8, TNSF12, GSTM1 and ME3 genes correlates with receptor tyrosine-protein kinase erbB-2 amplification (HER2)/estrogen receptor (ESR)/progesterone receptor (PR) status in primary BC tumors. Moreover, upon comparing differentially methylated WA responsive target genes with DNA methylation changes in different clinical subtypes of breast cancer patients in the cancer genome atlas (TCGA), we found that WA silences HER2/PR/ESR-dependent gene expression programs to suppress aggressive TNBC characteristics in favor of luminal BC hallmarks, with an improved therapeutic sensitivity. In this respect, WA may represent a novel and attractive phyto-pharmaceutical for TNBC treatment.
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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.