DNA-dependent protein kinase and ataxia telangiectasia mutated (ATM) promote cell survival in response to NK314, a topoisomerase IIα inhibitor.

ABSTRACT: 4-Hydroxy-5-methoxy-2,3-dihydro-1H-[1,3]benzodioxolo[5,6-c]pyrrolo[1,2-f]-phenanthridium chloride (NK314) is a benzo[c] phenanthridine alkaloid that inhibits topoisomerase IIα, leading to the generation of DNA double-strand breaks (DSBs) and activating the G(2) checkpoint pathway. The purpose of the present studies was to investigate the DNA intercalating properties of NK314, to evaluate the DNA repair mechanisms activated in cells that may lead to resistance to NK314, and to develop mechanism-based combination strategies to maximize the antitumor effect of the compound. A DNA unwinding assay indicated that NK314 intercalates in DNA, a property that likely cooperates with its ability to trap topoisomerase IIα in its cleavage complex form. The consequence of this is the formation of DNA DSB

SUBMITTER: Guo L 

PROVIDER: S-EPMC3141888 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature