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

S Kapitza; Michael Jakupec; Maria Uhl; Bernhard Keppler; Brigitte Marian

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

S Kapitza, Michael Jakupec, Maria Uhl, Bernhard Keppler, Brigitte Marian (Corresponding author)

Department of Inorganic Chemistry

Publications: Contribution to journal › Article › Peer Reviewed

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 mikroM. Both effects were prevented by 5 mM N-acetylcysteine (NAC) which also reduced cytotoxicity (IC50 55 vs 30 mikroM 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. ? 2005 Elsevier Ireland Ltd. All rights reserved.

Original language	English
Pages (from-to)	115-121
Number of pages	7
Journal	Cancer Letters
Volume	226
Issue number	2
Publication status	Published - 2005

Austrian Fields of Science 2012

301904 Cancer research

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title = "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 mikroM. Both effects were prevented by 5 mM N-acetylcysteine (NAC) which also reduced cytotoxicity (IC50 55 vs 30 mikroM 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. ? 2005 Elsevier Ireland Ltd. All rights reserved.",

author = "S Kapitza and Michael Jakupec and Maria Uhl and Bernhard Keppler and Brigitte Marian",

note = "DOI: 10.1016/j.canlet.2005.01.002 Coden: CALED Affiliations: Institute of Cancer Research, Medical University Vienna, Borschkegasse 8a, A 1090 Vienna, Austria; Institute of Inorganic Chemistry, University of Vienna, Vienna, Austria Adressen: Marian, B.; Institute of Cancer Research; Medical University Vienna; Borschkegasse 8a A 1090 Vienna, Austria; email: [email protected] Source-File: ChemieErgScopus.csv Import aus Scopus: 2-s2.0-22844452813 Importdatum: 09.01.2007 14:08:30 12.02.2008: Datenanforderung 2112 (Import Sachbearbeiter) 09.02.2010: Datenanforderung UNIVIS-DATEN-DAT.RA-2 (Import Sachbearbeiter)",

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language = "English",

volume = "226",

pages = "115--121",

journal = "Cancer Letters",

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T1 - The heterocyclic ruthenium(III) complex KP1019 (FFC14A) causes DNA damage and oxidative stress in colorectal tumor cells

AU - Kapitza, S

AU - Jakupec, Michael

AU - Uhl, Maria

AU - Keppler, Bernhard

AU - Marian, Brigitte

N1 - DOI: 10.1016/j.canlet.2005.01.002 Coden: CALED Affiliations: Institute of Cancer Research, Medical University Vienna, Borschkegasse 8a, A 1090 Vienna, Austria; Institute of Inorganic Chemistry, University of Vienna, Vienna, Austria Adressen: Marian, B.; Institute of Cancer Research; Medical University Vienna; Borschkegasse 8a A 1090 Vienna, Austria; email: [email protected] Source-File: ChemieErgScopus.csv Import aus Scopus: 2-s2.0-22844452813 Importdatum: 09.01.2007 14:08:30 12.02.2008: Datenanforderung 2112 (Import Sachbearbeiter) 09.02.2010: Datenanforderung UNIVIS-DATEN-DAT.RA-2 (Import Sachbearbeiter)

PY - 2005

Y1 - 2005

N2 - 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 mikroM. Both effects were prevented by 5 mM N-acetylcysteine (NAC) which also reduced cytotoxicity (IC50 55 vs 30 mikroM 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. ? 2005 Elsevier Ireland Ltd. All rights reserved.

AB - 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 mikroM. Both effects were prevented by 5 mM N-acetylcysteine (NAC) which also reduced cytotoxicity (IC50 55 vs 30 mikroM 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. ? 2005 Elsevier Ireland Ltd. All rights reserved.

M3 - Article

SN - 0304-3835

VL - 226

SP - 115

EP - 121

JO - Cancer Letters

JF - Cancer Letters

IS - 2

ER -

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

Abstract

Austrian Fields of Science 2012

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