Abstract:
:The CDC25 cell cycle regulators are promising targets for new pharmacologic approaches in cancer therapy. Inhibitory compounds such as BN82685 have proven to be effective in specifically targeting CDC25 in cultured cells and in inhibiting tumor cell growth. Here, we report that BN82685 impairs microtubule dynamic instability and alters microtubule organization and assembly at the centrosome in interphase cells. Treatment of mitotic cells with BN82685 delays mitotic spindle assembly, chromosome capture, and metaphase plate formation. Furthermore, we show that combining low concentrations of both BN82685 and paclitaxel inhibits the proliferation of HT29 human colon cancer cells. Our results show a role for CDC25 phosphatases in regulating microtubule dynamics throughout the cell cycle and suggest that combinations of CDC25 inhibitors with microtubule-targeting agents may be of therapeutic value.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Cazales M,Boutros R,Brezak MC,Chaumeron S,Prevost G,Ducommun Bdoi
10.1158/1535-7163.MCT-06-0299subject
Has Abstractpub_date
2007-01-01 00:00:00pages
318-25issue
1eissn
1535-7163issn
1538-8514pii
6/1/318journal_volume
6pub_type
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