Bidentate Ligands on Osmium(VI) Nitrido Complexes Control Intracellular Targeting and Cell Death Pathways

摘要

The cellular response evoked by anti-proliferating osmium(VI) nitrido compounds of general formula OsN(N^N)Cl3 (N^N = 2,2′-bipyridine >1, 1,10-phenanthroline >2, 3,4,7,8-tetramethyl-1,10-phenanthroline >3, or 4,7-diphenyl-1,10-phenanthroline >4) can be tuned by subtle ligand modifications. Complex 2 induces DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase, and caspase-dependent apoptotic cell death. In contrast, >4 evokes ER stress leading to the upregulation of proteins of the unfolded protein response pathway, increase in ER size, and p53-independent apoptotic cell death. To the best of our knowledge, >4 is the first osmium compound to induce ER stress in cancer cells.