Osmium carbonyl clusters containing labile ligands hyperstabilize microtubules.
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.
Department of Chemistry, National University of Singapore, Kent Ridge, Singapore 117543.
Kien Voon
KV
Kong
Weng Kee
WK
Leong
Lina H K
LH
Lim
D000818:Animals; D017209:Apoptosis; D002417:Cattle; D045744:Cell Line, Tumor; D004228:Dithionitrobenzoic Acid / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000633:toxicity; D009992:Osmium / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000378:metabolism
D008024:Ligands; D009942:Organometallic Compounds; D012710:Serum Albumin, Bovine; D009992:Osmium; D004228:Dithionitrobenzoic Acid; D016650:Fluorescein-5-isothiocyanate