Bidentate Ligands on Osmium(VI) Nitrido Complexes Control Intracellular Targeting and Cell Death Pathways
The cellular response evoked by antiproliferating osmium(VI) nitrido compounds of general formula OsN(N[superscript N])Cl[subscript 3] (N[superscript 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 subtl...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Chemical Society (ACS)
2015
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| Online Access: | http://hdl.handle.net/1721.1/95478 https://orcid.org/0000-0002-2693-4982 https://orcid.org/0000-0003-3383-0118 |
| Summary: | The cellular response evoked by antiproliferating osmium(VI) nitrido compounds of general formula OsN(N[superscript N])Cl[subscript 3] (N[superscript 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. |
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