DNA (cytosine-5)-methyltransferase (DNMT)

DNA (cytosine-5)-methyltransferases (DNMTs) are a family of enzymes, including DNMT1, DNMT3A, and DNMT3B, that catalyze the transfer of a methyl group from S-adenosyl-L-methionine to the C5 position of cytosine residues in DNA [1, 6]. This epigenetic modification, primarily occurring at CpG dinucleotides, is essential for gene silencing, genomic imprinting, X-chromosome inactivation, and maintaining chromosomal stability [2, 9]. In many cancers, aberrant overexpression or hyperactivity of DNMTs leads to the hypermethylation and subsequent silencing of tumor suppressor genes, such as p16 and GSTP1, which contributes to tumor progression and therapeutic resistance [3, 13]. Hydralazine, originally an antihypertensive vasodilator, has been identified as a non-nucleoside DNMT inhibitor that can reverse these epigenetic changes [4, 10]. It acts by either directly binding to the DNMT catalytic site or by downregulating the expression of DNMT1 and DNMT3A, thereby promoting DNA demethylation and the reactivation of silenced genes [7, 18]. While hydralazine offers a potentially less toxic alternative to nucleoside analogs like decitabine, its use is associated with the risk of drug-induced lupus erythematosus, a condition linked to the hypomethylation of T-cell DNA [11, 16].

Other names

DNA methyltransferaseDNA MTaseDNMT1DNMT3ADNMT3BCytosine-5 methyltransferase

Inhibition of DNA methyltransferase activity, leading to DNA hypomethylation and reactivation of silenced tumor suppressor genes [3, 4].