What is 2'-Deoxycytidine?

2'-Deoxycytidine is a pyrimidine 2'-deoxyribonucleoside with cytosine as the nucleobase and the ribose lacking a hydroxyl group at position 2. Deoxycytidine is involved in the methylation process, where a methyl group is attached to certain residues of DNA, but when deoxycytidine is present, it prevents the enzyme responsible for methylation from working properly. This results in insufficient chromosomal methylation. 2'-Deoxycytidine is essential for the synthesis of nucleic acids and can be used in cancer research.

What is 5-aza-2′-deoxycytidine?

5-aza-2′-deoxycytidine (5-aza) is a pyrimidine analog that reverses DNA methylation. It is incorporated into DNA during DNA replication and becomes a potent inhibitor of methyltransferases. Studies have shown that 5-aza-2'-deoxycytidine is more potent than 5-azacytidine in vivo . At high doses, these drugs are cytotoxic to cancer cells, but at lower concentrations, they reduce DNA methylation and reactivate target gene expression. 5-aza is often used in anticancer therapy with the histone deacetylase (HDAC) inhibitor trichostatin A to inhibit DNA methylation and histone modifications, respectively.

Side effects

Studies have found that 5-aza-2′-deoxycytidine drugs (decitabine, 5-azaCdR) have strong cytotoxic effects and can cause cancer cells and telomeres to lengthen rapidly during treatment. This can cause tumors to evolve into more aggressive forms and become resistant to the drugs originally used to treat them. In addition, 5-azaCdR has been reported to cause DNA hypomethylation and strong dose-dependent disruption of spermatogenesis. 5-azaCdR treatment has adverse effects on sperm motility and survival of offspring embryos at the blastocyst stage.

References:

[1] 5-aza-2′-deoxycytidine induces telomere dysfunction in breast cancer cells[J]. Biomedicine & Pharmacotherapy, 2024. DOI:10.1016/j.biopha.2024.117173.