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Bidentate ligands on osmium(VI) nitrido complexes control intracellular targeting and cell death pathways.

ABSTRACT: The cellular response evoked by antiproliferating 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 endoplasmic reticulum (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.

SUBMITTER: Suntharalingam K

PROVIDER: S-EPMC3791136 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Bidentate ligands on osmium(VI) nitrido complexes control intracellular targeting and cell death pathways.

Suntharalingam Kogularamanan K Johnstone Timothy C TC Bruno Peter M PM Lin Wei W Hemann Michael T MT Lippard Stephen J SJ

Journal of the American Chemical Society 20130916 38

The cellular response evoked by antiproliferating 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 endoplasmic reticulum (ER) stress lea ...[more]

PMID: 24041161

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