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

Cancer Lett. 2005 Aug 26;226(2):115-21. doi: 10.1016/j.canlet.2005.01.002.

Abstract

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 microm. Both effects were prevented by 5mM N-acetylcysteine (NAC) which also reduced cytotoxicity (IC(50) 55 vs 30 microM without NAC). Induction of apoptosis was shown 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.

MeSH terms

  • Acetylcysteine / pharmacology
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Collagen Type XI / drug effects
  • Collagen Type XI / metabolism
  • Colorectal Neoplasms / metabolism*
  • DNA Damage / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Indazoles / pharmacology*
  • Mitochondria / drug effects
  • Organometallic Compounds
  • Oxidative Stress / drug effects*
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Ruthenium Compounds / pharmacology*

Substances

  • COL11A2 protein, human
  • Collagen Type XI
  • Indazoles
  • Organometallic Compounds
  • Ruthenium Compounds
  • indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III))
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Acetylcysteine