Osmium carbonyl clusters containing labile ligands hyperstabilize microtubules

Abstract

A study into the possible molecular targets of the osmium carbonyl cluster Os3(CO) 10(NCCH 3) 2 (2) in the ER- breast carcinoma (MDA-MB-231) cell line was carried out. Infrared and 1H 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. © 2009 American Chemical Society.