The interaction between lipid derivatives of colchicine and tubulin: Consequences of the interaction of the alkaloid with lipid membranes

Colchicine is a potent antimitotic poison which is well known to prevent mi crotubule assembly by binding tubulin very tightly. Colchicine also possess es anti-inflammatory properties which are not well understood yet. Here we show that colchicine tightly interacts with lipid layers. The physical and biological properties of three different lipid derivatives of colchicine ar e investigated parallel to those of membrane lipids in the presence of colc hicine, Upon insertion in the fatty alkyl chains, colchicine rigidifies the lipid monolayers in a fluid phase and fluidifies rigid monolayers. Similar ly X-ray diffraction data show that lecithin-water phases are destabilized by colchicine. In addition, an unexpectedly drastic enhancement of the phot oisomerization rate of colchicine into lumicolchicine in the lipid environm ent is observed and further supports insertion of the alkaloid in membranes . Finally the interaction of colchicine with lipids makes the drug inaccess ible to tubulin. The possible in vivo significance of these results is disc ussed. (C) 2000 Elsevier Science B.V. All rights reserved.