Re-emerging antimetabolites with novel mechanism of action with respect to epigenetic regulation: Basic aspects

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Azacitidine (AzaC) and decitabine (DAC) are epigenetic modulators, which are used for treatment of several hematological malignancies. The epigenetic mode of action of these compounds comprises reduction of DNA methylation by inhibition of DNA methyltransferases (DNMTs), which include the maintenance DNA methyltransferase 1 and de novo methyltransferase DNMT3A and DNMT3B. This property leads to a decrease in CpG island methylation and a reactivation of tumor suppressor genes that are silenced by promoter hypermeth- ylation, thereby contributing to the anti-tumor effect. Insight in the mechanisms of action of these drugs is essential for our understanding how synthetic epigenetic modulators can affect cellular processes. In this review the intracellular metabolism of these cytidine analogs and some novel cytidine analogs are summarized. In addition, the mechanism of DNMT downregulation is discussed, which besides the incorporation of modified nucleotides into the DNA, more recently was also shown to involve proteasomal degradation.

Original languageEnglish
Title of host publicationChemotherapy for Leukemia
Subtitle of host publicationNovel Drugs and Treatment
PublisherSpringer Singapore
Number of pages16
ISBN (Electronic)9789811033322
ISBN (Print)9789811033308
Publication statusPublished - 17 Apr 2017


  • Azacitidine
  • Cancer
  • DNA methyltransferase
  • Decitabine

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