ArticleCancer prevention research (Philadelphia, Pa.)2008
Long-term epigenetic therapy with oral zebularine has minimal side effects and prevents intestinal tumors in mice.
Article in Cancer prevention research (Philadelphia, Pa.), 2008. 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, 99 citations in OpenAlex.
- Reversal of dual epigenetic repression of non-canonical Wnt-5a normalises diabetic corneal epithelial wound healing and stem cells.Diabetologia · 2023Article
- Insights into the Inhibitory Mechanisms of the Covalent Drugs for DNMT3A.International journal of molecular sciences · 2023Article
- Epigenetic modulation of antitumor immunity and immunotherapy response in breast cancer: biological mechanisms and clinical implications.Frontiers in immunology · 2023Review
- The Protective Effect of Zebularine, an Inhibitor of DNA Methyltransferase, on Renal Tubulointerstitial Inflammation and Fibrosis.International journal of molecular sciences · 2022Article
- 5-Aza-4'-thio-2'-deoxycytidine, a New Orally Bioavailable Nontoxic "Best-in-Class": DNA Methyltransferase 1-Depleting Agent in Clinical Development.The Journal of pharmacology and experimental therapeutics · 2021Review
- DNA Methylation Patterns inEnvironmental health perspectives · 2021Article
- Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation.Molecules (Basel, Switzerland) · 2018Review
- Inhibition of DNA Methylation Suppresses Intestinal Tumor Organoids by Inducing an Anti-Viral Response.Scientific reports · 2016Article
- Chromatin deregulation in disease.Chromosoma · 2016Review
- Epigenetic impact of infection on carcinogenesis: mechanisms and applications.Genome medicine · 2016Review
- Prospects for the development of epigenetic drugs for CNS conditions.Nature reviews. Drug discovery · 2015Review
- Demethylating drugs as novel analgesics for cancer pain.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Targeted Cox2 gene deletion in intestinal epithelial cells decreases tumorigenesis in female, but not male, ApcMin/+ mice.Molecular oncology · 2014Article
- DNA methyltransferase inhibitors improve the effect of chemotherapeutic agents in SW48 and HT-29 colorectal cancer cells.PloS one · 2014Article
- DNA methylation and cancer diagnosis.International journal of molecular sciences · 2013Review
- Zebularine regulates early stages of mESC differentiation: effect on cardiac commitment.Cell death & disease · 2013Article
- Increased CDA expression/activity in males contributes to decreased cytidine analog half-life and likely contributes to worse outcomes with 5-azacytidine or decitabine therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Hypomethylating therapy in an aggressive stroma-rich model of pancreatic carcinoma.Cancer research · 2013Article
- Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells.Cancer biology & therapy · 2012Article
- DNA methyltransferase inhibitor, zebularine, delays tumor growth and induces apoptosis in a genetically engineered mouse model of breast cancer.Molecular cancer therapeutics · 2012Article
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10 authors at 4 institutions in 1 country.
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Abstract
Recent successes in the application of epigenetic drugs for the treatment of myelodysplastic syndrome have raised questions on the safety of long-term administration of DNA methylation inhibitors. We treated preweaned cancer prone Apc(Min/+) (Min) mice continuously with the DNA methylation inhibitor zebularine in their drinking water to determine the effects of the drug on normal mouse development as well as cancer prevention. Zebularine caused a tissue-specific reduction in DNA methylation at B1 short interspersed nucleotide elements in the small and large intestines of female Min mice but not in other organs examined after chronic oral treatment. No significant difference in the average weights of mice was observed during the treatment. In addition, analysis of global gene expression of colonic epithelial cells from the females indicated that only 3% to 6% of the genes were affected in their expression. We did not detect toxicity and abnormalities from the histopathologic analysis of liver and intestinal tissues. Lastly, we tested whether prevention of tumorigenesis can be achieved with chronic oral administration of zebularine in Min mice. The average number of polyps in Min females decreased from 58 to 1, whereas the average polyp number remained unaffected in Min males possibly due to differential activity of aldehyde oxidase. Taken together, our results show for the first time that long-term oral administration of zebularine causes a gender-specific abrogation of intestinal tumors while causing a tissue-specific DNA demethylation. Importantly, prolonged treatment of mice with epigenetic drugs resulted in only minor developmental and histologic changes.
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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.