The heterocyclic ruthenium(III) complex KP1019 (FFC14A) causes DNA damage and oxidative stress in colorectal tumor cells

The Ru(III) complex salt KP1019 induced formation of H2O2 in colorectal tumor cells in a dose-dependent way. It also caused DNA-strand breaks if only weakly doubling tail length to 55.87 +/- 3.97 mu m. Both effects were prevented by 5 mM N-acetylcysteine (NAG) which also reduced cytotoxicity (IC50 55 vs 30 mu M without NAC). Induction of apoptosis was show by loss of mitochondrial membrane potential in 63.4 +/- 2.1% of the population and by caspase-dependent cleavage of poly-(ADP-ribose)-polymerase (PARP). Both effects were inhibited by NAC which reduced the population with depolarized mitochondrial membranes to 24.1 +/- 1.2% and prevented PARP-cleavage indicating a central role oxidative stress in KP1019-induced apoptosis. (C) 2005 Elsevier Ireland Ltd. All rights reserved.