Effects of 5-Aza-2'-deoxycytidine (decitabine) on gene expression.

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Seelan RS, Mukhopadhyay P, Pisano MM, Greene RM

Effects of 5-Aza-2'-deoxycytidine (decitabine) on gene expression.

Drug Metab Rev. 2018 May;50(2):193-207. doi: 10.1080/03602532.2018.1437446. Epub 2018 Feb 18.

PubMed ID

29455551 [ View in PubMed

]

Abstract

5-Aza-2'-deoxycytidine (AzaD), also known as Decitabine, is a deoxycytidine analog that is typically used to activate methylated and silenced genes by promoter demethylation. However, a survey of the scientific literature indicates that promoter demethylation may not be the only (or, indeed, the major) mechanism by which AzaD affects gene expression. Regulation of gene expression by AzaD can occur in several ways, including some that are independent of DNA demethylation. Results from several studies indicate that the effect of AzaD on gene expression is highly context-dependent and can differ for the same gene under different environmental settings. This may, in part, be due to the nature of the silencing mechanism(s) involved - DNA methylation, repressive histone modifications, or a combination of both. The varied effects of AzaD on such context-dependent regulation of gene expression may underlie some of the diverse responses exhibited by patients undergoing AzaD therapy. In this review, we describe the salient properties of AzaD with particular emphasis on its diverse effects on gene expression, aspects that have barely been discussed in most reviews of this interesting drug.

DrugBank Data that Cites this Article

Drugs

Decitabine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Decitabine	DNA	Nucleotide	Humans	Yes	Other/unknown	Details
Decitabine	DNA (cytosine-5)-methyltransferase 1	Protein	Humans	Yes	Inhibitor	Details
Decitabine	DNA (cytosine-5)-methyltransferase 3A	Protein	Humans	Unknown	Inhibitor	Details
Decitabine	DNA (cytosine-5)-methyltransferase 3B	Protein	Humans	Unknown	Inhibitor	Details

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Decitabine	Cytidine deaminase	Protein	Humans	No	Substrate	Details
Decitabine	Deoxycytidine kinase	Protein	Humans	Yes	Substrate	Details
Decitabine	Nucleoside diphosphokinase (Protein Group)	Protein group	Humans	Yes	Substrate	Details
Decitabine	UMP-CMP kinase	Protein	Humans	Yes	Substrate	Details

Drug Reactions

Reaction
Decitabine DB01262 Deoxycytidine kinase 5-aza-2'-deoxycytidine-monophosphate DBMET03187	Details
Decitabine DB01262 Cytidine deaminase 5-aza-2'-deoxyuridine DBMET03190	Details