Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on microtubules in vitro.

Abstract

The Vinca alkaloids differ in their chemotherapeutic effectiveness and their toxicities. To determine whether differences are due to a differential effect on the assembly of tubulin into microtubules, we examined the effects of vincristine, vinblastine, and a newer alkaloid, desacetyl vinblastine amide, on the assembly of bovine brain tubulin in vitro. The three compounds block bovine tubulin polymerization in vitro and almost equally effectively at a 1 muM concentration (tubulin, 6.5 muM). At 10 muM, the three alkaloids also interact with preformed microtubules in vitro, causing spiral-like distortions of the microtubules. No effect of the alkaloids on polymerization of another fibrous protein, actin, was observed. Thus the differential actions of vinblastine, vincristine, and desacetyl vinblastine amide in vivo seems to be based on some biological process other than the reaction with tubulin or the microtubules per se.