Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2′-deoxycytidine

Molecular Cancer Therapeutics - Tập 4 Số 10 - Trang 1515-1520 - 2005
Jody C. Chuang1, Christine B. Yoo2, Jennifer M. Kwan3, Tony W.H. Li2, Gangning Liang2, Allen S. Yang3, Peter A. Jones2
1USC/Norris Comprehensive Cancer Center, Department of Urology, Biochemistry, and Molecular Biology, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA.
21USC/Norris Comprehensive Cancer Center, Department of Urology, Biochemistry, and Molecular Biology and
32Department of Medicine, Division of Hematology, Keck School of Medicine, University of Southern California, Los Angeles, California

Tóm tắt

AbstractDNA cytosine methylation plays a considerable role in normal development, gene regulation, and carcinogenesis. Hypermethylation of the promoters of some tumor suppressor genes and the associated silencing of these genes often occur in certain cancer types. The reversal of this process by DNA methylation inhibitors is a promising new strategy for cancer therapy. In addition to the four well-characterized nucleoside analogue methylation inhibitors, 5-azacytidine, 5-aza-2′-deoxycytidine (5-Aza-CdR), 5-fluoro-2′-deoxycytidine, and zebularine, there is a growing list of non-nucleoside inhibitors. However, a systemic study comparing these potential demethylating agents has not been done. In this study, we examined three non-nucleoside demethylating agents, (−)-epigallocatechin-3-gallate, hydralazine, and procainamide, and compared their effects and potencies with 5-Aza-CdR, the most potent DNA methylation inhibitor. We found that 5-Aza-CdR is far more effective in DNA methylation inhibition as well as in reactivating genes, compared with non-nucleoside inhibitors.

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Molecular Cancer Therapeutics

Tập 4 Số 10

1515-1520

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