Nucleolar targeting by platinum: p53-independent apoptosis follows rRNA inhibition, cell-cycle arrest, and DNA compaction.

ABSTRACT: TriplatinNC is a highly positively charged, substitution-inert derivative of the phase II clinical anticancer drug, BBR3464. Such substitution-inert complexes form a distinct subset of polynuclear platinum complexes (PPCs) interacting with DNA and other biomolecules through noncovalent interactions. Rapid cellular entry is facilitated via interaction with cell surface glycosoaminoglycans and is a mechanism unique to PPCs. Nanoscale secondary ion mass spectrometry (nanoSIMS) showed rapid distribution within cytoplasmic and nucleolar compartments, but not the nucleus. In this article, the downstream effects of nucleolar localization are described. In human colon carcinoma cells, HCT116, the production rate of 47S rRNA precursor transcripts was dramatically reduced as an early event after dru

SUBMITTER: Peterson EJ 

PROVIDER: S-EPMC4334294 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature