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. (Cancer Res 2005; 65(8):
3040-3)