Neutral metalloaminopeptidases APN and MetAP2 as newly discovered anticancer molecular targets of actinomycin D and its simple analogs.

ABSTRACT: The potent transcription inhibitor Actinomycin D is used with several cancers. Here, we report the discovery that this naturally occurring antibiotic inhibits two human neutral aminopeptidases, the cell-surface alanine aminopeptidase and intracellular methionine aminopeptidase type 2. These metallo-containing exopeptidases participate in tumor cell expansion and motility and are targets for anticancer therapies. We show that the peptide portions of Actinomycin D and Actinomycin X₂ are not required for effective inhibition, but the loss of these regions changes the mechanism of interaction. Two structurally less complex Actinomycin D analogs containing the phenoxazone chromophores, Questiomycin A and Actinocin, appear to be competitive inhibitors of both aminopeptidases, with pot

SUBMITTER: Weglarz-Tomczak E 

PROVIDER: S-EPMC6047675 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature