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Highly cytotoxic substitutionally inert rhodium(III) tris(chelate) complexes: DNA binding modes and biological impact on human cancer cells

The antiproliferative properties and cellular impact of novel substitutionally inert rhodium(III) complexes of the types [Rh{(CH3)2 NCS2}2(pp)]Cl 3-5 (pp=5,6-Me2phen, dpq, dppz) and OC-6-23-[Rh(2-S-py)2(pp)]Cl 6 and 7 (2-S-py=pyridine-2-thiolate; pp=dpq, dppz) have been investigated for the adherent...

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Main Authors: Hackenberg, Frauke (Author) , Oehninger, Luciano (Author) , Alborzinia, Hamed (Author) , Can, Suzan (Author) , Kitanovic, Igor (Author) , Geldmacher, Yvonne (Author) , Kokoschka, Malte (Author) , Wölfl, Stefan (Author) , Ott, Ingo (Author) , Sheldrick, William S. (Author)
Format: Article (Journal)
Language:English
Published: 21 April 2011
In: Journal of inorganic biochemistry
Year: 2011, Volume: 105, Issue: 7, Pages: 991-999
ISSN:1873-3344
DOI:10.1016/j.jinorgbio.2011.04.006
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jinorgbio.2011.04.006
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0162013411000936
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Author Notes:Frauke Hackenberg, Luciano Oehninger, Hamed Alborzinia, Suzan Can, Igor Kitanovic, Yvonne Geldmacher, Malte Kokoschka, Stefan Wölfl, Ingo Ott, William S. Sheldrick
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Summary:The antiproliferative properties and cellular impact of novel substitutionally inert rhodium(III) complexes of the types [Rh{(CH3)2 NCS2}2(pp)]Cl 3-5 (pp=5,6-Me2phen, dpq, dppz) and OC-6-23-[Rh(2-S-py)2(pp)]Cl 6 and 7 (2-S-py=pyridine-2-thiolate; pp=dpq, dppz) have been investigated for the adherent human cancer cell lines MCF-7 and HT-29 and for non-adherent Jurkat cells. Whereas CD and viscosity measurements indicate that the polypyridyl ligands of 4 and 5 intercalate into CT DNA, this is not the case for the analogous pyridine-2-thiolate complexes 6 and 7. Complexes 3-7 all exhibit a high antiproliferative activity towards MCF-7 and HT-29 cells, with IC50 values in the range 0.055-0.285μM. As established by online monitoring with a cell-based sensor chip, the highly cytostatic complex 6 (IC50=0.059 and 0.078μM) invokes an immediate concentration-dependent reduction of MCF-7 cell respiration and a time-delayed decrease in cellular impedance, which can be ascribed to the induction of cell death. Annexin V/PI assays demonstrated that 6 also has a pronounced antiproliferative activity towards Jurkat cells and that it invokes extensive apoptosis and high concentrations of reactive oxygen species in these leukemia cells. The observation of a dose-dependent inhibition of the oxygen consumption of isolated mice mitochondria indicates the involvement of an intrinsic mitochondrial pathway in this process.
Item Description:Gesehen am 26.07.2022
Physical Description:Online Resource
ISSN:1873-3344
DOI:10.1016/j.jinorgbio.2011.04.006

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