Journal
BIOMETALS
Volume 24, Issue 4, Pages 645-661Publisher
SPRINGER
DOI: 10.1007/s10534-011-9414-9
Keywords
Rhodium; Thiacrown ether; Cytotoxicity; Leukemia; Apoptosis; ROS
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG) [FOR 630]
- Ruhr University Research School
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The cytostatic properties of novel rhodium(III) thiacrown ether complexes [RhCl(LL)([9]aneS(3))](n+) with either aromatic kappa(2) N ligands (n = 2) or anionic chelate ligands (n = 1) have been investigated for the human cancer cell lines HT-29 and MCF-7 and for immortalized HEK-293 cells. Taken together with literature IC50 values for analogous complexes with polypyridyl ligands or 1,4-dithiane, the in vitro assays indicate that dicationic complexes with soft kappa(2) N (imino) or kappa(2) S (thiaether) ligands exhibit significantly higher antiproliferative effects than those with hard kappa(2) N (amino) ligands. Dicationic complexes are more active than monocationic complexes with similar ligands. Pronounced apoptosis-inducing properties towards Jurkat cells were established for complexes with LL = bpm, dpq, and 1,4-dithiane. The order of activity (bpm > 1,4-dithiane > dpq > bpy) contrasts to that observed for adhesive cancer cells (bpm > bpy, 1,4-dithiane > dpq). Necrosis is insignificant in all cases. The percentage of Jurkat cells exhibiting apoptosis after 24 or 48 h incubation periods is directly correlated to the percentage of cells exhibiting high levels of reactive oxygen species. As established by online monitoring with a sensor chip system, treatment of MCF-7 cells with the bpm and 1,4-dithiane complexes leads to a significant and permanent concentration-dependent decrease in oxygen consumption and cellular adhesion.
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