Nanaomycin A selectively inhibits DNMT3B and reactivates silenced tumor suppressor genes in human cancer cells.
Mol Cancer Ther
; 9(11): 3015-23, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-20833755
ABSTRACT
Enzymes involved in the epigenetic regulation of the genome represent promising starting points for therapeutic intervention by small molecules, and DNA methyltransferases (DNMT) are emerging targets for the development of a new class of cancer therapeutics. In this work, we present nanaomycin A, initially identified by a virtual screening for inhibitors against DNMT1, as a compound inducing antiproliferative effects in three different tumor cell lines originating from different tissues. Nanaomycin A treatment reduced the global methylation levels in all three cell lines and reactivated transcription of the RASSF1A tumor suppressor gene. In biochemical assays, nanaomycin A revealed selectivity toward DNMT3B. To the best of our knowledge, this is the first DNMT3B-selective inhibitor identified to induce genomic demethylation. Our study thus establishes the possibility of selectively inhibiting individual DNMT enzymes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Transcricional
/
Genes Supressores de Tumor
/
Naftoquinonas
/
DNA (Citosina-5-)-Metiltransferases
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Mol Cancer Ther
Assunto da revista:
ANTINEOPLASICOS
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Alemanha