ArticlePloS one2012
ING1 and 5-azacytidine act synergistically to block breast cancer cell growth.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- Quantitative Proteomics and Molecular Mechanisms of Non-Hodgkin Lymphoma Mice Treated with Incomptine A, Part II.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Oxidative Stress: The Role of Antioxidant Phytochemicals in the Prevention and Treatment of Diseases.International journal of molecular sciences · 2024Review
- Molecular mechanisms of inhibitor of growth (ING) family members in health and malignancy.Cancer cell international · 2022Review
- mRNA and protein of p33ING1 in normal and cancer tissues.Translational cancer research · 2020Article
- Biological Functions of the ING Proteins.Cancers · 2019Review
- 1,25(OH)Cell proliferation · 2018Article
- ING5 suppresses breast cancer progression and is regulated by miR-24.Molecular cancer · 2017Article
- INGs are potential drug targets for cancer.Journal of cancer research and clinical oncology · 2017Review
- A Comparative Study on the In Vitro Effects of the DNA Methyltransferase Inhibitor 5-Azacytidine (5-AzaC) in Breast/Mammary Cancer of Different Mammalian Species.Journal of mammary gland biology and neoplasia · 2016Review
- A minimal ING1b fragment that improves the efficacy of HDAC-based cancer cell killing.Cell death & disease · 2015Article
- DNA demethylation and invasive cancer: implications for therapeutics.British journal of pharmacology · 2015Review
- Defining the minimal peptide sequence of the ING1b tumour suppressor capable of efficiently inducing apoptosis.Cell death discovery · 2015Article
- Reduced ING1 levels in breast cancer promotes metastasis.Oncotarget · 2014Article
- Tumor cell apoptosis mediated by cytoplasmic ING1 is associated with improved survival in oral squamous cell carcinoma patients.Oncotarget · 2014Article
- ING1 and ING2: multifaceted tumor suppressor genes.Cellular and molecular life sciences : CMLS · 2013Review
- ING1 induces apoptosis through direct effects at the mitochondria.Cell death & disease · 2013Article
- Src regulates the activity of the ING1 tumor suppressor.PloS one · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundInhibitor of Growth (ING) proteins are epigenetic "readers" that recognize trimethylated lysine 4 of histone H3 (H3K4Me3) and target histone acetyl transferase (HAT) and histone deacetylase (HDAC) complexes to chromatin. METHODS AND PRINCIPAL
findingsHere we asked whether dysregulating two epigenetic pathways with chemical inhibitors showed synergistic effects on breast cancer cell line killing. We also tested whether ING1 could synergize better with chemotherapeutics that target the same epigenetic mechanism such as the HDAC inhibitor LBH589 (Panobinostat) or a different epigenetic mechanism such as 5-azacytidine (5azaC), which inhibits DNA methyl transferases. Simultaneous treatment of breast cancer cell lines with LBH589 and 5azaC did not show significant synergy in killing cells. However, combination treatment of ING1 with either LBH589 or 5azaC did show synergy. The combination of ING1b with 5azaC, which targets two distinct epigenetic mechanisms, was more effective at lower doses and enhanced apoptosis as determined by Annexin V staining and cleavage of caspase 3 and poly-ADP-ribose polymerase (PARP). ING1b plus 5azaC also acted synergistically to increase γH2AX staining indicating significant levels of DNA damage were induced. Adenoviral delivery of ING1b with 5azaC also inhibited cancer cell growth in a murine xenograft model and led to tumor regression when viral concentration was optimized in vivo.
conclusionsThese data show that targeting distinct epigenetic pathways can be more effective in blocking cancer cell line growth than targeting the same pathway with multiple agents, and that using viral delivery of epigenetic regulators can be more effective in synergizing with a chemical agent than using two chemotherapeutic agents. This study also indicates that the ING1 epigenetic regulator may have additional activities in the cell when expressed at high levels.
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