VINBLASTINE SUPPRESSES DYNAMICS OF INDIVIDUAL MICROTUBULES IN LIVING INTERPHASE CELLS

We have characterized the effects of vinblastine on the dynamic instab ility behavior of individual microtubules in living BS-C-1 cells micro injected with rhodamine-labeled tubulin and have found that at low con centrations (3-64 nM), vinblastine potently suppresses dynamic instabi lity without causing net microtubule depolymerization. Vinblastine sup pressed the rates of microtubule growth and shortening, and decreased the frequency of transitions from growth or pause to shortening, also called catastrophe. In vinblastine-treated cells, both the average dur ation of a pause (a state of attenuated dynamics where neither growth nor shortening could be detected) and the percentage of total time spe nt in pause were significantly increased. Vinblastine potently decreas ed dynamicity, a measure of the overall dynamic activity of microtubul es, reducing this parameter by 75% at 32 nM. The present work, consist ent with earlier in vitro studies, demonstrates that vinblastine kinet ically caps the ends of microtubules in living cells and supports the hypothesis that the potent chemotherapeutic action of vinblastine as a n antitumor drug is suppression of mitotic spindle microtubule dynamic s. Further, the results indicate that molecules that bind to microtubu le ends can regulate microtubule dynamic behavior in living cells and suggest that endogenous regulators of microtubule dynamics that work b y similar mechanisms may exist in living cells.