DNA-intercalators causing rapid re-expression of methylated and silenced genes in cancer cells.

ABSTRACT: Epigenetic inactivation of tumor-suppressor and other regulatory genes plays a critical role in carcinogenesis. Transcriptional silencing is often maintained by DNA methyl transferase (DNMT)-mediated hypermethylation of CpG islands in promoter DNA. Nucleoside analogs including azacytidine and decitabine have been used to inhibit DNMT and re-activate genes, and are clinically used. Their shortcomings include a short half-life and a slow onset of action due to required nucleotide incorporation during DNA replication, which may limit clinical utility. It might be useful to begin to identify lead compounds having novel properties, specifically distinct and fast-acting gene desilencing. We previously identified chemicals augmenting gene expression in multiple reporter systems. We now report tha

SUBMITTER: Hossain MZ 

PROVIDER: S-EPMC3712575 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature