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

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.

• Authors: Susanne Kapitza, Michael A Jakupec, Maria Uhl, Bernhard K Keppler, Brigitte Marian
• Journal: Cancer letters (Cancer Lett) Vol. 226 Issue 2 Pg. 115-21 (Aug 26 2005) ISSN: 0304-3835 [Print] Ireland
• PMID: 16039951 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• Acetylcysteine (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Collagen Type XI (drug effects, 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)