Specific inhibition of DNMT1/CFP1 reduces cancer phenotypes and enhances chemotherapy effectiveness

Epigenomics. 2014 Jun;6(3):267-75. doi: 10.2217/epi.14.18.

Abstract

Aim: DNA methylation is a fundamental biologic process of genomes and is a candidate for pharmacological manipulation that might have important therapeutic advantages. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug intervention.

Materials & methods: To develop a new generation of DNMT inhibitor, we analyzed the ability of peptides to selectively inhibit certain DNMT1-incuding complexes.

Results: Our study demonstrates that the disruption of DNMT1/CFP1-including complexes increases the efficiency of chemotherapeutic treatment on established tumors in mice.

Conclusion: Our data opens a promising and innovative alternative to the development of DNMT inhibitors.

Keywords: DNA methylation; DNMT inhibitor; DNMT1; cell death; epigenetic; glioblastoma; glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors*
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology*
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / drug therapy
  • Glioma / pathology*
  • Mice
  • Neoplasm Transplantation
  • Peptides / pharmacology*
  • Temozolomide
  • Trans-Activators / antagonists & inhibitors*

Substances

  • Cxxc1 protein, mouse
  • Enzyme Inhibitors
  • Peptides
  • Trans-Activators
  • Dacarbazine
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • Dnmt1 protein, mouse
  • Temozolomide