Ceratamines, structurally simple microtubule-stabilizing antimitotic agents with unusual cellular effects.
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.
Karjala
Geoffrey
G
Department of Biochemistry and Molecular Biology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Chan
Queenie
Q
Manzo
Emiliano
E
Andersen
Raymond J
RJ
Roberge
Michel
M
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001381:Azepines / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects*
D000970:Antineoplastic Agents; D001381:Azepines; D007093:Imidazoles; C485389:ceratamine A; C485390:ceratamine B