ArticleEpigenetics2012
Modifying metabolically sensitive histone marks by inhibiting glutamine metabolism affects gene expression and alters cancer cell phenotype.
Article in Epigenetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 80 citations in OpenAlex.
- Histone modifications across cancers: mechanisms, therapy and clinical translation.Molecular cancer · 2026Review
- Genomic Perspective on Heterogeneity of Organs and Body Aging.Aging cell · 2026Review
- Review
- Chronic Ammonia Stress in Chinese Perch (Antioxidants (Basel, Switzerland) · 2025Article
- Glutamine-mediated epigenetic regulation of cFLIP underlies resistance to TRAIL in pancreatic cancer.Experimental & molecular medicine · 2024Article
- The causes and consequences of trained immunity in myeloid cells.Frontiers in immunology · 2024Review
- Glutaminase - A potential target for cancer treatment.BioMedicine · 2024Review
- Metabolomics combined with mathematical analysis reveals metabolic pathways specific to metastatic cancers.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2024Article
- The Interplay between Dysregulated Metabolism and Epigenetics in Cancer.Biomolecules · 2023Review
- Ovarian Cancer and Glutamine Metabolism.International journal of molecular sciences · 2023Review
- Comprehensive Analysis Reveals the Potential Roles of CDKN3 in Pancancer and Verification in Endometrial Cancer.International journal of general medicine · 2023Article
- Overview of Cancer Metabolism and Signaling Transduction.International journal of molecular sciences · 2022Review
- Connections between metabolism and epigenetics: mechanisms and novel anti-cancer strategy.Frontiers in pharmacology · 2022Review
- Understanding the Crosstalk Between Epigenetics and Immunometabolism to Combat Cancer.Sub-cellular biochemistry · 2022Article
- Metabolic Regulation of Lysine Acetylation: Implications in Cancer.Sub-cellular biochemistry · 2022Review
- Modulation of DNA/RNA Methylation Signaling Mediating Metabolic Homeostasis in Cancer.Sub-cellular biochemistry · 2022Review
- Relationship between metabolic reprogramming and drug resistance in breast cancer.Frontiers in oncology · 2022Review
- A glutamine 'tug-of-war': targets to manipulate glutamine metabolism for cancer immunotherapy.Immunotherapy advances · 2021Review
- Oxidation of Energy Substrates in Tissues of Fish: Metabolic Significance and Implications for Gene Expression and Carcinogenesis.Advances in experimental medicine and biology · 2021Article
- Modeling the Th17 and Tregs Paradigm: Implications for Cancer Immunotherapy.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interplay of metabolism and epigenetic regulatory mechanisms has become a focal point for a better understanding of cancer development and progression. In this study, we have acquired data supporting previous observations that demonstrate glutamine metabolism affects histone modifications in human breast cancer cell lines. Treatment of non-invasive epithelial (T-47D and MDA-MB-361) and invasive mesenchymal (MDA-MB-231 and Hs-578T) breast cancer cell lines with the glutaminase inhibitor, Compound 968, resulted in cytotoxicity in all cell lines, with the greatest effect being observed in MDA-MB-231 breast cancer cells. Compound 968-treatment induced significant downregulation of 20 critical cancer-related genes, the majority of which are anti-apoptotic and/or promote metastasis, including AKT, BCL2, BCL2L1, CCND1, CDKN3, ERBB2, ETS1, E2F1, JUN, KITLG, MYB, and MYC. Histone H3K4me3, a mark of transcriptional activation, was reduced at the promoters of all but one of these critical cancer genes. The decrease in histone H3K4me3 at global and gene-specific levels correlated with reduced expression of SETD1 and ASH2L, genes encoding the histone H3K4 methyltransferase complex. Further, the expression of other epigenetic regulatory genes, known to be downregulated during apoptosis (e.g., DNMT1, DNMT3B, SETD1 and SIRT1), was also downregulated by Compound 968. These changes in gene expression and histone modifications were accompanied by the activation of apoptosis, and decreased invasiveness and resistance of MDA-MB-231 cells to chemotherapeutic drug doxorubicin. The results of this study provide evidence to a link between cytotoxicity caused by inhibiting glutamine metabolism with alterations of the epigenome of breast cancer cells and suggest that modification of intracellular metabolism may enhance the efficiency of epigenetic therapy.
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