Antiproliferative effects and DNA hypomethylation by 5-aza-2'-deoxycytidine in human neuroblastoma cell lines.
5-Aza-2'-deoxycytidine (5-AZA-CdR) is an inhibitor of DNA methylation, and its antileukemic activity has been shown in preclinical and clinical studies. This paper describes the ability of 5-AZA-CdR to inhibit DNA methylation, DNA synthesis and cell growth in several human neuroblastoma cell lines. The stability of cell growth inhibition was ascertained, as well as the ability of the metabolite thymidine to enhance the antiproliferative effect of 5-AZA-CdR. The activity of phosphorylating enzyme deoxycytidine kinase (dCK) was correlated to different levels of sensitivity in several cell lines. The results obtained indicate that 5-AZA-CdR may be an agent for the chemotherapy of neuroblastoma.
Carpinelli
P
P
Dipartimento di Chimica Organica e Biologica, Università di Napoli Federico II, Italy.
Granata
F
F
Augusti-Tocco
G
G
Rossi
M
M
Bartolucci
S
S
D000943:Antigens, Differentiation; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000378:metabolism*; D015257:DNA-Cytosine Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D003841:Deoxycytidine; D003842:Deoxycytidine Kinase / Q000037:antagonists & inhibitors; D006801:Humans; D008745:Methylation; D009447:Neuroblastoma / Q000188:drug therapy* / Q000276:immunology; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D003841:Deoxycytidine; D000077209:Decitabine; D015257:DNA-Cytosine Methylases; D003842:Deoxycytidine Kinase; D001374:Azacitidine