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Research Articles: Therapeutics, Targets, and Development

Pharmacologic inhibition of CDC25 phosphatases impairs interphase microtubule dynamics and mitotic spindle assembly

¹ LBCMCP-CNRS UMR5088-IFR109, Université Paul Sabatier, Toulouse, France and ² IPSEN, Institut Henri Beaufour, Les Ulis, France

Requests for reprints: Bernard Ducommun, LBCMCP-CNRS UMR5088-IFR109, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse, France. Phone: 33-56155-6210; Fax: 33-56155-8109. E-mail: ducommun{at}cict.fr.

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. [Mol Cancer Ther 2007;6(1):318–25]

Grant support: Centre National de la Recherche Scientifique, l'Université Paul Sabatier and la Ligue Nationale Contre le Cancer (Equipe labellisée 2005) to B. Ducommun.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 5/22/06; revised 10/ 6/06; accepted 11/17/06.

This article has been cited by other articles:

				R. Boutros, V. Lobjois, and B. Ducommun CDC25B Involvement in the Centrosome Duplication Cycle and in Microtubule Nucleation Cancer Res., December 15, 2007; 67(24): 11557 - 11564. [Abstract] [Full Text] [PDF]