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Bidentate ligands on osmium(VI) nitrido complexes control intracellular targeting and cell death pathways.
Suntharalingam, Kogularamanan; Johnstone, Timothy C; Bruno, Peter M; Lin, Wei; Hemann, Michael T; Lippard, Stephen J.
Afiliación
  • Suntharalingam K; Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
J Am Chem Soc ; 135(38): 14060-3, 2013 Sep 25.
Article en En | MEDLINE | ID: mdl-24041161
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osmio / Fenantrolinas / 2,2'-Dipiridil / Proteína p53 Supresora de Tumor / Complejos de Coordinación / Antineoplásicos Límite: Humans Idioma: En Revista: J Am Chem Soc Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osmio / Fenantrolinas / 2,2'-Dipiridil / Proteína p53 Supresora de Tumor / Complejos de Coordinación / Antineoplásicos Límite: Humans Idioma: En Revista: J Am Chem Soc Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos