Histone deacetylase inhibition overcomes drug resistance through a miRNA-dependent mechanism.

ABSTRACT: The treatment of specific tumor cell lines with poly- and oligoamine analogs results in a superinduction of polyamine catabolism that is associated with cytotoxicity; however, other tumor cells show resistance to analog treatment. Recent data indicate that some of these analogs also have direct epigenetic effects. We, therefore, sought to determine the effects of combining specific analogs with an epigenetic targeting agent in phenotypically resistant human lung cancer cell lines. We show that the histone deacetylase inhibitor MS-275, when combined with (N(1), N(11))-bisethylnorspermine (BENSpm) or (N(1), N(12))-bis(ethyl)-cis-6,7-dehydrospermine tetrahydrochloride (PG-11047), synergistically induces the polyamine catabolic enzyme spermidine/spermine N(1)-acetyltransferase (SSAT), a major

SUBMITTER: Murray-Stewart T 

PROVIDER: S-EPMC3808125 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature