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  • Title: Dual functions of iridium(III) 2-phenylpyridine complexes: Metastasis inhibition and lysosomal damage.
    Author: Liu X, Chen S, Ge X, Zhang Y, Xie Y, Hao Y, Wu D, Zhao J, Yuan XA, Tian L, Liu Z.
    Journal: J Inorg Biochem; 2020 Apr; 205():110983. PubMed ID: 31954343.
    Abstract:
    Six N-phenylcarbazole/triphenylamine-appended half-sandwich iridium(III) 2-phenylpyridine complexes ([(η5-Cp*)Ir(C^N)Cl]) were prepared and characterized. Compared with cisplatin, these complexes exhibited potential antitumor activity against A549 and HeLa tumor cells, with IC50 values (half-maximum inhibitory concentration) that changed from 2.8 ± 0.8 μM to 39.5 ± 2.7 μM, and could block the migration of tumor cells. These complexes also effectively bound to protein (binding constant: ~104 M-1) and were transported through serum proteins, catalyzed the oxidation of coenzyme nicotinamide-adenine dinucleotide. Additionally, laser confocal microscopy and flow cytometry confirmed that these complexes possessed a non-energy-dependent cellular uptake mechanism, effectively accumulated in lysosomes (Pearson colocalization coefficient: ~0.74), damaged the integrity of acidic lysosomes, led to a change in the mitochondrial membrane potential, disrupted the cell cycle (G0/G1 phase), and eventually induced apoptosis. Above all, these complexes are potential antitumor agents with dual functions: metastasis inhibition and lysosomal damage.
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