Metal-Based Inhibition of Poly(ADP-ribose) Polymerase - The Guardian Angel of DNA
The inhibition activity of a series of anticancer metal complexes based on platinum, ruthenium, and gold metal ions was evaluated on the zinc-finger protein PARP-1, either purified or directly on protein extracts from human breast cancer MCF7 cells. Information on the reactivity of the metal complexes with the PARP-1 zinc-finger domain was obtained by high-resolution ESI FT-ICR mass spectrometry. An excellent correlation between PARP-1 inhibition in protein extracts and the ability of the complexes to bind to the zinc-finger motif (in competition with zinc) was established. The results support a model whereby displacement of zinc from the PARP-1 zinc finger by other metal ions leads to decreased PARP-1 activity. In vitro combination studies of cisplatin with NAMI-A and RAPTA-T on different cancer cell lines (MCF7, A2780, and A2780cisR) showed that, in some cases, a synergistic effect is in operation.
Keywords: Organometallic Ruthenium Compound ; Platinum-Modified Dna ; Mass-Spectrometry ; Anticancer Drugs ; Solution Chemistry ; Nuclear Proteins ; Zinc Fingers ; Gold(Iii) Complexes ; Binding Properties ; Bipyridyl Ligands
Record created on 2011-05-12, modified on 2016-08-09