Taxol induces the assembly of free microtubules in living cells and blocks the organizing capacity of the centrosomes and kinetochores.
Taxol, a potent promoter of microtubule polymerization in vitro, induces massive assembly of free microtubules in cultured cells as visualized by immunocytochemistry and electron microscopy. The centrosomes and kinetochores largely lost their capacity to organize microtubule assembly, as became evident by the disappearance of the cytoplasmic microtubule complex and the mitotic spindle. The taxol-induced microtubules were partially resistant to nocodazole, an inhibitor of tubulin polymerization. Moreover, taxol induced microtubule assembly in cells pretreated with nocodazole. Increasing the ratio of nocodazole to taxol restored the ability of the centrosomes and kinetochores to specifically induce microtubule assembly in their immediate vicinity. The data suggest that taxol lowers the critical tubulin concentration in vivo as well as in vitro and that the organizing capacity of the microtubule-organizing centers depends on the cytoplasmic polymerization threshold.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001562:Benzimidazoles / Q000037:antagonists & inhibitors; D002219:Carbamates / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D002502:Centrioles / Q000187:drug effects*; D002503:Centromere / Q000187:drug effects*; D002875:Chromosomes / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects; D015739:Nocodazole; D009940:Organoids / Q000187:drug effects*; D017239:Paclitaxel; D011485:Protein Binding / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D001562:Benzimidazoles; D002219:Carbamates; D014404:Tubulin; D017239:Paclitaxel; D015739:Nocodazole