Journal
CANCER CELL
Volume 6, Issue 2, Pages 151-158Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2004.06.023
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Funding
- NCI NIH HHS [T32 CA09659, R01 CA 82422] Funding Source: Medline
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The frequent silencing of tumor suppressor genes by altered cytosine methylation and chromatin structural changes makes this process an attractive target for epigenetic therapy. Here we show that zebularine, a stable DNA cytosine methylation inhibitor, is preferentially incorporated into DNA and exhibits greater cell growth inhibition and gene expression in cancer cell lines compared to normal fibroblasts. In addition, zebularine preferentially depleted DNA methyltransferase 1 (DNMT1) and induced expression of cancer-related antigen genes in cancer cells relative to normal fibroblasts. Our results demonstrate that zebularine can be selective toward cancer cells and may hold clinical promise as an anticancer therapy.
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