癌细胞对泽布勒林的优先反应。

Preferential response of cancer cells to zebularine.

作者信息

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

机构信息

USC/Norris Comprehensive Cancer Center, Departments of Urology, Biochemistry, and Molecular Biology, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA.

出版信息

Cancer Cell. 2004 Aug;6(2):151-8. doi: 10.1016/j.ccr.2004.06.023.

DOI:10.1016/j.ccr.2004.06.023

PMID:15324698

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.

摘要

肿瘤抑制基因常常因胞嘧啶甲基化改变和染色质结构变化而沉默，这使得该过程成为表观遗传治疗的一个有吸引力的靶点。在此我们表明，zebularine是一种稳定的DNA胞嘧啶甲基化抑制剂，与正常成纤维细胞相比，它优先掺入DNA，并在癌细胞系中表现出更强的细胞生长抑制作用和基因表达。此外，相对于正常成纤维细胞，zebularine在癌细胞中优先消耗DNA甲基转移酶1（DNMT1）并诱导癌症相关抗原基因的表达。我们的结果表明，zebularine对癌细胞具有选择性，作为一种抗癌疗法可能具有临床应用前景。