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)
|