Journal of Molecular Medicine

, 85:1137 | Cite as

Potential advantages of DNA methyltransferase 1 (DNMT1)-targeted inhibition for cancer therapy

  • Yeonjoo Jung
  • Jinah Park
  • Tai Young Kim
  • Jung-Hyun Park
  • Hyun-Soon Jong
  • Seock-Ah Im
  • Keith D. Robertson
  • Yung-Jue Bang
  • Tae-You Kim
Original Article


The deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor 5-aza-2′-deoxycytidine (5-aza-dC) has been used as a drug in a part of cancer therapy. However, because of its incorporation into DNA during DNA synthesis, 5-aza-dC can cause DNA damage, mutagenesis, and cytotoxicity. In view of the adverse effects of 5-aza-dC, DNMT-targeted inhibition may be a more effective approach than treatment with 5-aza-dC. To address the possibility of DNMT-targeted cancer therapy, we compared the effects of treatment with small interfering ribonucleic acids (siRNAs) specific for DNMT1 or DNMT3b and treatment with 5-aza-dC on transcription, cell growth, and DNA damage in gastric cancer cells. We found that DNMT1-targeted inhibition induced the re-expression and reversed DNA methylation of five (CDKN2A, RASSF1A, HTLF, RUNX3, and AKAP12B) out of seven genes examined, and 5-aza-dC reactivated and demethylated all seven genes. In contrast, DNMT3b siRNAs did not show any effect. Furthermore, the double knockdown of DNMT1 and DNMT3b did not show a synergistic effect on gene re-expression and demethylation. In addition, DNMT1 siRNAs showed an inhibitory effect of cell proliferation in the cancer cells and the induction of cell death without evidence of DNA damage, whereas treatment with 5-aza-dC caused DNA damage as demonstrated by the comet assay. These results provide a rationale for the development of a DNMT1-targeted strategy as an effective epigenetic cancer therapy.


Epigenetic gene silencing Promoter hypermethylation DNA methyltransferase siRNAs 5-aza-dC 



DNA methyltransferase




small interfering RNA



This work was supported in part by grants from the Korean Ministry of Science and Technology through the National Research Laboratory Program for Cancer Epigenetics (No. M10400000336-06J0000-33610), and BK21 Project for Medicine, Dentistry and Pharmacy.

Supplementary material

109_2007_216_MOESM1_ESM.pdf (181 kb)
Supplementary Table 1 Primer sequences for RT-PCR analysis (PDF 180 KB)
109_2007_216_MOESM2_ESM.pdf (130 kb)
Supplementary Table 2 Primer sequences for MS-PCR analysis (PDF 130 KB)
109_2007_216_MOESM3_ESM.pdf (96 kb)
Supplementary Figure 1 (PDF 96.1 KB)
109_2007_216_MOESM4_ESM.pdf (23 kb)
Supplementary Figure 2 (PDF 22.8 KB)


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Yeonjoo Jung
    • 1
  • Jinah Park
    • 1
  • Tai Young Kim
    • 1
  • Jung-Hyun Park
    • 1
  • Hyun-Soon Jong
    • 1
  • Seock-Ah Im
    • 1
    • 2
  • Keith D. Robertson
    • 3
  • Yung-Jue Bang
    • 1
    • 2
  • Tae-You Kim
    • 1
    • 2
  1. 1.National Research Laboratory for Cancer Epigenetics, Cancer Research InstituteSeoul National University College of MedicineSeoulSouth Korea
  2. 2.Department of Internal MedicineSeoul National University College of MedicineSeoulSouth Korea
  3. 3.Department of Biochemistry and Molecular BiologyUniversity of FloridaGainesvilleUSA

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