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[Cancer Research 65, 3040-3043, April 15, 2005]
© 2005 American Association for Cancer Research

Priority Reports

Ceratamines, Structurally Simple Microtubule-Stabilizing Antimitotic Agents with Unusual Cellular Effects

Geoffrey Karjala1, Queenie Chan1, Emiliano Manzo2, Raymond J. Andersen2 and Michel Roberge1

Departments of 1 Biochemistry and Molecular Biology and 2 Chemistry and Oceanography (EOS), University of British Columbia, Vancouver, British Columbia, Canada

Requests for reprints: Michel Roberge, Department of Biochemistry and Molecular Biology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3. Phone: 604-822-2304; Fax: 604-822-5227; Email: michelr{at}interchange.ubc.ca.

Ceratamine A and ceratamine B are heterocyclic alkaloids recently identified in a screen for compounds that arrest cells in mitosis. Treatment of breast carcinoma MCF-7 cells causes a concentration-dependent block of cell cycle progression exclusively at mitosis. In vitro studies with purified tubulin indicate that the ceratamines directly stimulate microtubule polymerization in the absence of microtubule-associated proteins. Cells treated with ceratamines show a dense perinuclear microtubule network in interphase and multiple pillar-like tubulin structures in mitotic cells. The ceratamines do not compete with paclitaxel for binding to microtubules in vitro. Unlike other microtubule-stabilizing agents, the ceratamines have simple structures with no chiral centers, making them attractive drug leads.




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[Abstract] [Full Text] [PDF]


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Copyright © 2005 by the American Association for Cancer Research.