Osmium carbonyl clusters containing labile ligands hyperstabilize microtubules.

Abstract

A study into the possible molecular targets of the osmium carbonyl cluster Os(3)(CO)(10)(NCCH(3))(2) (2) in the ER- breast carcinoma (MDA-MB-231) cell line was carried out. Infrared and (1)H NMR analyses of cells treated with 2 showed the formation of carboxylato- and thiolato-bridged clusters from the interaction with intracellular carboxylic acid and sulfhydryl residues. The cytotoxicity of 2 was reduced in the presence of fetal bovine serum, and measurement with Ellman's reagent as well as fluorescence confocal microscopy with tetramethylrhodamine-5-maleimide staining all demonstrated binding to intracellular sulfhydryl groups leading up to cell disruption. Tubulin-FITC antibody staining of treated cells showed disruption of the microtubules, and a tubulin polmerization assay showed that 2 induced hyperstabilization of the microtubules.

• Authors: Kien Voon Kong, Weng Kee Leong, Lina H K Lim
• Journal: Chemical research in toxicology (Chem Res Toxicol) Vol. 22 Issue 6 Pg. 1116-22 (Jun 2009) ISSN: 1520-5010 [Electronic] United States
• PMID: 19441774 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• Organometallic Compounds
• Serum Albumin, Bovine
• Osmium
• Dithionitrobenzoic Acid
• Fluorescein-5-isothiocyanate

Topics

• Animals
• Apoptosis
• Cattle
• Cell Line, Tumor
• Dithionitrobenzoic Acid (chemistry)
• Fluorescein-5-isothiocyanate (chemistry)
• Humans
• Ligands
• Microscopy, Fluorescence
• Microtubules (metabolism)
• Organometallic Compounds (chemistry, toxicity)
• Osmium (chemistry)
• Serum Albumin, Bovine (metabolism)