Faculty Bibliography

Taxol, an experimental antitumor agent and stabilizer of microtubules, inhibits in vitro replication of the human pathogenic hemoflagellate Trypanosoma cruzi. Micromolar concentrations of the drug prevent the completion of cell division in these organisms but allow the multiplication of cell organelles such as the nucleus, kinetoplast, and flagellum. The result is the formation of motile organisms that have extra organelles but cannot fully replicate. Division proceeds to a relatively fixed locus on the long axis of the organism, suggesting the presence of a specific affected structure or function at this site. It is postulated that taxol produces these effects by stabilizing a portion of the microtubular cytoskeleton of T. cruzi

Taxol increases the rate and extent of microtubule assembly in vitro and stabilizes microtubules in vitro and in cells [Schiff, P. B., Fant, J., & Horwitz, S. B. (1979) Nature (London) 277, 665-667; Schiff, P. B., & Horwitz, S. B. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 1561-1565]. We report herein that taxol has the ability to promote microtubule assembly in the absence of microtubule-associated proteins, rings, and added guanosine 5'-triphosphate (GTP or organic buffer. The drug enhances additional microtubule assembly when added to microtubules at apparent steady state. This additional assembly can be attributed to both elongation of existing microtubules and spontaneous nucleation of new microtubules. Taxol-treated microtubules have depressed dissociation reactions as determined by dilution experiments. The drug does not inhibit the binding of GTP or the hydrolysis of GTP or guanosine 5'-diphosphate (GDP) in our microtubule protein preparations. Taxol does not competitively inhibit the binding of colchicine to tubulin

Taxol, a potent inhibitor of human HeLa and mouse fibroblast cell replication, blocked cells in the G2 and M phase of the cell cycle and stabilized cytoplasmic microtubules. The cytoplasmic microtubules of taxol-treated cells were visualized by transmission electron microscopy and indirect immunofluorescence microscopy. More than 90% of the cells treated with 10 micro M taxol for 22 hr at 37 degrees C displayed bundles of microtubules that appeared to radiate from a common site (or sites), in addition to their cytoplasmic microtubules. Untreated cells that were kept in the cold (4 degrees C) for 16 hr lost their microtubules, whereas cells that were pretreated with taxol for 22 hr at 37 degrees C continued to display their microtubules and bundles of microtubules in the cold. Taxol inhibited the migration behavior of fibroblast cells, but these cells did not lose their ability to produce mobile surface projections such as lamellipodia and filopodia