title: Inhibition of cell migration and cell division correlates with distinct effects of microtubule inhibiting drugs.
abstract: Drugs that target microtubules are thought to inhibit cell division and cell migration by suppressing dynamic instability, a "search and capture" behavior that allows microtubules to probe their environment. Here, we report that subtoxic drug concentrations are sufficient to inhibit plus-end microtubule dynamic instability and cell migration without affecting cell division or microtubule assembly. The higher drug concentrations needed to inhibit cell division act through a novel mechanism that generates microtubule fragments by stimulating microtubule minus-end detachment from their organizing centers. The frequency of microtubule detachment in untreated cells increases at prophase suggesting that it is a regulated cellular process important for spindle assembly and function. We conclude that drugs produce differential dose-dependent effects at microtubule plus and minus-ends to inhibit different microtubule-mediated functions.
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School, Houston, Texas 77030, USA.
authors.forename: Hailing
authors.initials: H
authors.lastname: Yang
authors.forename: Anutosh
authors.initials: A
authors.lastname: Ganguly
authors.forename: Fernando
authors.initials: F
authors.lastname: Cabral
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000187:drug effects; D019556:COS Cells / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D018385:Centrosome / Q000378:metabolism; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D003703:Demecolcine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D008869:Microtubule-Associated Proteins; D014404:Tubulin; D050257:Tubulin Modulators; D014747:Vinblastine; D003703:Demecolcine