Re-emerging Antimetabolites with Novel Mechanism of Action with Respect to Epigenetic Regulation: Basic Aspects View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2017

AUTHORS

Dzjemma Sarkisjan , Renske D. M. Steenbergen , Jacqueline Cloos , Godefridus J. Peters

ABSTRACT

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 hypermethylation, 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. More... »

PAGES

311-326

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  • Book

    TITLE

    Chemotherapy for Leukemia

    ISBN

    978-981-10-3330-8
    978-981-10-3332-2

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/978-981-10-3332-2_18

    DOI

    http://dx.doi.org/10.1007/978-981-10-3332-2_18

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1084913612


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