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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| Hauptverfasser: | , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
21 April 2011
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| In: |
Journal of inorganic biochemistry
Year: 2011, Jahrgang: 105, Heft: 7, Pages: 991-999 |
| ISSN: | 1873-3344 |
| DOI: | 10.1016/j.jinorgbio.2011.04.006 |
| Online-Zugang: | 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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| Verfasserangaben: | 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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| 245 | 1 | 0 | |a Highly cytotoxic substitutionally inert rhodium(III) tris(chelate) complexes |b DNA binding modes and biological impact on human cancer cells |c 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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| 264 | 1 | |c 21 April 2011 | |
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| 520 | |a 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. | ||
| 650 | 4 | |a Anticancer agents | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Cell metabolism | |
| 650 | 4 | |a DNA binding | |
| 650 | 4 | |a Polypyridyl ligands | |
| 650 | 4 | |a Rhodium | |
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