Microtubule-destabilizing agents: structural and mechanistic insights from the interaction of colchicine and vinblastine with tubulin.

Microtubules (MTs) are dynamic structures of the eukaryotic cytoskeleton that, during cell division, form the mitotic spindle. Perturbing them leads to mitotic arrest and ultimately to cell death. Consistently, MTs and their building block, αß tubulin, are one of the best characterized targets in anti-cancer chemotherapy. Drugs that interfere with MTs either stabilize or destabilize them. The latter class is the subject of this review. These ligands bind to the colchicine site or to the vinca domain, two distinct sites located at a distance from each other on tubulin. Nevertheless the effects of both classes of ligands share a common theme, they prevent the formation of MT specific contacts, therefore triggering their disassembly.