Preferential response of cancer cells to zebularine

Jonathan C. Cheng, Christine B. Yoo, Daniel J. Weisenberger, Jody Chuang, Chandra Wozniak, Gangning Liang, Victor E. Marquez, Sheldon Greer, Torben F. Orntoft, Thomas Thykjaer, Peter A. Jones

Research output: Contribution to journalArticle

238 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalCancer Cell
Volume6
Issue number2
DOIs
StatePublished - Aug 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Cheng, J. C., Yoo, C. B., Weisenberger, D. J., Chuang, J., Wozniak, C., Liang, G., Marquez, V. E., Greer, S., Orntoft, T. F., Thykjaer, T., & Jones, P. A. (2004). Preferential response of cancer cells to zebularine. Cancer Cell, 6(2), 151-158. https://doi.org/10.1016/j.ccr.2004.06.023