Lysosome-targeted chemotherapeutics: Anticancer mechanism of N-heterocyclic carbene iridium(III) complex.

Lysosome-targeted chemotherapeutics: Anticancer mechanism of N-heterocyclic carbene iridium(III) complex. J Inorg Biochem. 2020 Mar 19;207:111063 Authors: Zhang J, Liu J, Liu X, Liu B, Song S, He X, Che C, Si M, Yang G, Liu Z Abstract N-heterocyclic carbenes-modified half-sandwich iridium(III) complex [(η5-C5Me4C6H4C6H5)Ir(C^C)Cl]PF6 (C1) (where C^C is a N-heterocyclic carbene ligand) can effectively prevent the proliferation of human cervical cancer cells. Here, this study aims to investigate the in-deep anticancer effects of this complex on non-small cell lung cancer cells and explore the underlying molecular mechanism. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed that iridium(III) complex had potent cytotoxicity studies towards non-small cell lung cancer cells (A549), human lung squamous cells (L78), human cervical cancer cells (Hela) and human bronchial epithelial cells (BEAS-2B). Colocalization and cellular uptake studies were analyzed by confocal microscopy. Notably, C1 targeted lysosomes and entered the cancer cells partially through an energy-dependent pathway, inducing the release of cathepsins and other proteins. These proteins regulated lysosomal-mitochondrial dysfunction, thus leading to the release of cytochrome c (cyt c), which amplified apoptotic signals by activating many downstream pathways such as caspase pathways to promote cell apoptosis. The results showed that the inhibitory m...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research