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.
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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)
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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
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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)
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