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Preferential response of cancer cells to zebularine

  1. Author:
    Cheng, J. C.
    Yoo, C. B.
    Weisenberger, D. J.
    Chuang, J.
    Wozniak, C.
    Liang, G. N.
    Marquez, V. E.
    Greer, S.
    Orntoft, T. F.
    Thykjaer, T.
    Jones, P. A.

  2. Author Address

    Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Urol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Mol Biol, Los Angeles, CA 90089 USA. NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. Univ Miami, Sch Med, Sylvester Canc Ctr, Dept Microbiol & Immunol, Miami, FL 33136 USA. Univ Miami, Sch Med, Sylvester Canc Ctr, Dept Biochem & Mol Biol, Miami, FL 33136 USA. Univ Miami, Sch Med, Sylvester Canc Ctr, Dept Radiat Oncol, Miami, FL 33136 USA. Aarhus Univ Hosp, Dept Clin Biochem, Mol Diagnost Lab, DK-8200 Aarhus N, Denmark Jones, PA, Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Urol, 1441 Eastlake Ave, Los Angeles, CA 90089 USA
    1. Year: 2004
    2. Date: AUG
  2. Journal: Cancer Cell
    1. 6
    2. 2
    3. Pages: 151-158
  4. Type of Article: Article
  1. 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

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External Sources

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  2. DOI: 10.1016/j.ccr.2004.06.023
  3. View record in Web of Science®
  4. WOS: 000223591900009

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