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Ceratamines, structurally simple microtubule-stabilizing antimitotic agents with unusual cellular effects

TitleCeratamines, structurally simple microtubule-stabilizing antimitotic agents with unusual cellular effects
Publication TypeJournal Article
Year of Publication2005
AuthorsKarjala, G, Chan, Q, Manzo, E, Andersen, RJ, Roberge, N
JournalCancer Research
Volume65
Pagination3040-3043
Date PublishedApr
Type of ArticleArticle
ISBN Number0008-5472
KeywordsBIND, CELLS, RESISTANT, TAXOID SITE, TUBULIN
Abstract

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.

URL<Go to ISI>://000228424800012