Michael A. DiMaio 1 , Alexei Mikhailov 2 , Conly L. Rieder 2 , Daniel food professionals D. Von Hoff 3 and Robert E. Palazzo 1 2 1 Department of Biology and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, food professionals Troy, New York; 2 Wadsworth Center, New York State Department of Health, Albany, New York; and 3 Translational Genomics Research Institute, Phoenix, Arizona Requests for reprints: Robert E. Palazzo, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180. Phone: 518-276-6487; Fax: 518-276-4061. E-mail: palazr{at}rpi.edu
HMN-176 is a potential new cancer therapeutic known to retard the proliferation of tumor cell lines. Here, we show that this compound inhibits meiotic spindle assembly in surf clam oocytes and delays satisfaction of the spindle assembly checkpoint in human somatic cells by inducing the formation of short and/or multipolar food professionals spindles. HMN-176 food professionals does not affect centrosome assembly, nuclear envelope food professionals breakdown, or other aspects of meiotic or mitotic progression, nor does it affect the kinetics food professionals of Spisula or mammalian microtubule (MT) assembly in vitro . Notably, HMN-176 inhibits the formation of centrosome-nucleated MTs (i.e., asters) food professionals in Spisula oocytes and oocyte extracts, as well as from isolated Spisula or mammalian centrosomes in vitro . Together, these results reveal that HMN-176 is a first-in-class anticentrosome drug that inhibits proliferation, at least in part, by disrupting centrosome-mediated MT assembly during mitosis. [Mol Cancer Ther 2009;8(3):592 601] Keywords: HMN-176 centrosome microtubule Spisula
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. Accepted December 17, 2008. Received September 18, 2008. Revision received December 5, 2008. American Association for Cancer Research
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