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: Kogularamanan Suntharalingam, Timothy C Johnstone, Peter M Bruno, Wei Lin, Michael T Hemann, Stephen J Lippard
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 135 Issue 38 Pg. 14060-3 (Sep 25 2013) ISSN: 1520-5126 [Electronic] United States
• PMID: 24041161 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Coordination Complexes
• Ligands
• Phenanthrolines
• Tumor Suppressor Protein p53
• Osmium
• 2,2'-Dipyridyl

Topics

• 2,2'-Dipyridyl (chemistry)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis
• Cell Line, Tumor
• Coordination Complexes (chemical synthesis, chemistry, pharmacology)
• DNA Damage
• Drug Screening Assays, Antitumor
• Endoplasmic Reticulum Stress
• G2 Phase Cell Cycle Checkpoints
• Humans
• Ligands
• M Phase Cell Cycle Checkpoints
• Osmium
• Phenanthrolines (chemistry)
• Signal Transduction
• Structure-Activity Relationship
• Tumor Suppressor Protein p53 (metabolism)