Osmium Carbonyl Clusters Containing Labile Ligands Hyperstabilize Microtubules

被引:37
|
作者
Kong, Kien Voon [1 ]
Leong, Weng Kee [1 ]
Lim, Lina H. K. [1 ]
机构
[1] Natl Univ Singapore, Dept Chem, Singapore 117543, Singapore
关键词
AMINO-ACID-SEQUENCE; ALPHA-BETA-TUBULIN; APOPTOSIS; TRIOSMIUM; TARGETS; BINDING; AGENTS; TAXOL;
D O I
10.1021/tx900056a
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A study into the possible molecular targets of the osmium carbonyl cluster Os-3(CO)(10)(NCCH3)(2) (2) in the ER-breast carcinoma (MDA-MB-231) cell line was carried out. Infrared and H-1 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.
引用
收藏
页码:1116 / 1122
页数:7
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