ArticleCell death & disease2015
NF-κB-dependent and -independent epigenetic modulation using the novel anti-cancer agent DMAPT.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- Novel therapeutic targets at the crossroad between epigenetics and signal transduction pathways in B-cell lymphomas.Clinical and experimental medicine · 2026Review
- NF-κB in inflammation and cancer.Cellular & molecular immunology · 2025Review
- NF-κB inhibition attenuates sympathetic hyperreflexia and concomitant development of autonomic dysreflexia and immune dysfunction after spinal cord injury.Communications biology · 2025Article
- The NF-κB signaling network in the life of T cells.Frontiers in immunology · 2025Review
- Identification of small molecules that are synthetically lethal upon knockout of the RNA ligase Rlig1 in human cells.RSC chemical biology · 2024Article
- Immune-related gene methylation prognostic instrument for stratification and targeted treatment of ovarian cancer patients toward advanced 3PM approach.The EPMA journal · 2024Article
- Revisiting Neuroblastoma: Nrf2, NF-κB and Phox2B as a Promising Network in Neuroblastoma.Current issues in molecular biology · 2024Review
- Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene.Cancer research communications · 2024Article
- Discovery of an effective anti-inflammatory agent for inhibiting the activation of NF-κB.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- H3 histone methylation landscape in male urogenital cancers: from molecular mechanisms to epigenetic biomarkers and therapeutic targets.Frontiers in cell and developmental biology · 2023Review
- Role of the inflammasome in insulin resistance and type 2 diabetes mellitus.Frontiers in immunology · 2023Review
- NF-κB mediated regulation of tumor cell proliferation in hypoxic microenvironment.Frontiers in pharmacology · 2023Review
- Revisiting Epithelial Carcinogenesis.International journal of molecular sciences · 2022Article
- The Emerging Potential of Parthenolide Nanoformulations in Tumor Therapy.Drug design, development and therapy · 2022Review
- Antitumor properties of novel sesquiterpene lactone analogs as NFκB inhibitors that bind to the IKKβ ubiquitin-like domain (ULD).European journal of medicinal chemistry · 2021Article
- PCA-based unsupervised feature extraction for gene expression analysis of COVID-19 patients.Scientific reports · 2021Article
- Mechanisms of Ataxia Telangiectasia Mutated (ATM) Control in the DNA Damage Response to Oxidative Stress, Epigenetic Regulation, and Persistent Innate Immune Suppression Following Sepsis.Antioxidants (Basel, Switzerland) · 2021Review
- Aniline-containing derivatives of parthenolide: Synthesis and anti-chronic lymphocytic leukaemia activity.Tetrahedron · 2020Article
- Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease.Scientific reports · 2020Article
- Parthenolide as Cooperating Agent for Anti-Cancer Treatment of Various Malignancies.Pharmaceuticals (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The transcription factor nuclear factor-kappaB (NF-κB) is constitutively active in several cancers and is a target of therapeutic development. We recently developed dimethylaminoparthenolide (DMAPT), a clinical grade water-soluble analog of parthenolide, as a potent inhibitor of NF-κB and demonstrated in vitro and in vivo anti-tumor activities in multiple cancers. In this study, we show DMAPT is an epigenetic modulator functioning in an NF-κB-dependent and -independent manner. DMAPT-mediated NF-κB inhibition resulted in elevated histone H3K36 trimethylation (H3K36me3), which could be recapitulated through genetic ablation of the p65 subunit of NF-κB or inhibitor-of-kappaB alpha super-repressor overexpression. DMAPT treatment and p65 ablation increased the levels of H3K36 trimethylases NSD1 (KMT3B) and SETD2 (KMT3A), suggesting that NF-κB directly represses their expression and that lower H3K36me3 is an epigenetic marker of constitutive NF-κB activity. Overexpression of a constitutively active p65 subunit of NF-κB reduced NSD1 and H3K36me3 levels. NSD1 is essential for DMAPT-induced expression of pro-apoptotic BIM, indicating a functional link between epigenetic modification and gene expression. Interestingly, we observed enhanced H4K20 trimethylation and induction of H4K20 trimethylase KMT5C in DMAPT-treated cells independent of NF-κB inhibition. These results add KMT5C to the list NF-κB-independent epigenetic targets of parthenolide, which include previously described histone deacetylase 1 (HDAC-1) and DNA methyltransferase 1. As NSD1 and SETD2 are known tumor suppressors and loss of H4K20 trimethylation is an early event in cancer progression, which contributes to genomic instability, we propose DMAPT as a potent pharmacologic agent that can reverse NF-κB-dependent and -independent cancer-specific epigenetic abnormalities.
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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.