title: 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.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Kogularamanan
authors.initials: K
authors.lastname: Suntharalingam
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Johnstone
authors.forename: Peter M
authors.initials: PM
authors.lastname: Bruno
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hemann
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D059865:Endoplasmic Reticulum Stress; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D008024:Ligands; D059566:M Phase Cell Cycle Checkpoints; D009992:Osmium; D010618:Phenanthrolines / Q000737:chemistry*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D010618:Phenanthrolines; D016159:Tumor Suppressor Protein p53; D009992:Osmium; D015082:2,2'-Dipyridyl
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