ArticleMolecular cancer therapeutics2012
DNA methyltransferase inhibitor, zebularine, delays tumor growth and induces apoptosis in a genetically engineered mouse model of breast cancer.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 64 citations in OpenAlex.
- Recent advances on gene-related DNA methylation in cancer diagnosis, prognosis, and treatment: a clinical perspective.Clinical epigenetics · 2025Review
- Article
- Zebularine showed anti-tumor efficacy in clear cell renal cell carcinoma.Frontiers in pharmacology · 2025Article
- Research progress and applications of epigenetic biomarkers in cancer.Frontiers in pharmacology · 2024Review
- The Protective Effect of Zebularine, an Inhibitor of DNA Methyltransferase, on Renal Tubulointerstitial Inflammation and Fibrosis.International journal of molecular sciences · 2022Article
- DNA methyltransferase 1 inhibits microRNA-497 and elevates GPRC5A expression to promote chemotherapy resistance and metastasis in breast cancer.Cancer cell international · 2022Article
- DNA Methylation Patterns inEnvironmental health perspectives · 2021Article
- Estrogen receptor α is involved in the regulation of ITGA8 methylation in estrogen receptor-positive breast cancer.Annals of translational medicine · 2020Article
- Investigation of the Effect of Zebularine in Comparison to and in Combination with Trichostatin A on p21Cip1/Waf1/ Sdi1, p27Kip1, p57Kip2, DNA Methyltransferases and Histone Deacetylases in Colon Cancer LS 180 Cell Line.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- The Inhibitory Effect of (-)-Epigallocatechin-3-Gallate on Breast Cancer Progression via ReducingMolecules (Basel, Switzerland) · 2019Article
- The DNA methyltransferase inhibitor zebularine exerts antitumor effects and reveals BATF2 as a poor prognostic marker for childhood medulloblastoma.Investigational new drugs · 2017Article
- Zebularine enhances apoptosis of human osteosarcoma cells by suppressing methylation of ARHI.Cancer science · 2016Article
- Epigenetic impact of infection on carcinogenesis: mechanisms and applications.Genome medicine · 2016Review
- Integrating genetics and epigenetics in breast cancer: biological insights, experimental, computational methods and therapeutic potential.BMC systems biology · 2015Review
- Prospects for the development of epigenetic drugs for CNS conditions.Nature reviews. Drug discovery · 2015Review
- Epigenetic treatment of solid tumours: a review of clinical trials.Clinical epigenetics · 2015Review
- Antimetabolite Treatment for Pancreatic Cancer.Chemotherapy · 2014Article
- RGS6 suppresses Ras-induced cellular transformation by facilitating Tip60-mediated Dnmt1 degradation and promoting apoptosis.Oncogene · 2014Article
- Zebularine-induced apoptosis in Calu-6 lung cancer cells is influenced by ROS and GSH level changes.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- DNA methylation dynamics in health and disease.Nature structural & molecular biology · 2013Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Zebularine is a novel potent inhibitor of both cytidine deaminase and DNA methylation. We examined the effect of zebularine on mammary tumor growth in genetically engineered MMTV-PyMT transgenic mice that develop mammary tumors at 60 days of age with 100% penetrance. The MMTV-PyMT transgenic mice were randomized at 46 days of age into control (n = 25) and zebularine (n = 25) treatment groups and monitored for parameters of tumor growth. Zebularine was administered at 5 mg/mL in drinking water. We observed a significant delay in the growth of mammary tumors in zebularine-treated mice with a statistically significant reduction (P = 0.0135) in total tumor burden at 94 days of age when the mice were sacrificed. After 48 days of zebularine treatment, the tumors were predominantly necrotic compared with untreated animals. In addition, a high apoptotic index by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was observed as early as 13 days following treatment. Immunoblot analysis showed depletion of DNMT1 and partial depletion of DNMT3b after zebularine treatment. Microarray analyses of global gene expression identified upregulation of twelve methylation-regulated genes as well as a set of candidate cancer genes that participate in cell growth and apoptosis. In summary, zebularine inhibits the growth of spontaneous mammary tumors and causes early onset of tumor cell necrosis and apoptosis in a genetically engineered mouse model of breast cancer. Defining the parameters of zebularine-mediated tumor inhibition may advance the future development of DNA methyltransferase inhibitors as an effective cancer treatment.
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