Taxol affects nuclear lamina and pore complex organization and inhibits import of karyophilic proteins into the cell nucleus

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dc.contributor.authorTheodoropoulos, P. A.en
dc.contributor.authorPolioudaki, H.en
dc.contributor.authorKostaki, O.en
dc.contributor.authorDerdas, S. P.en
dc.contributor.authorGeorgoulias, V.en
dc.contributor.authorDargemont, C.en
dc.contributor.authorGeorgatos, S. D.en
dc.date.accessioned2015-11-24T19:42:57Z
dc.date.available2015-11-24T19:42:57Z
dc.identifier.issn0008-5472-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/24709
dc.rightsDefault Licence-
dc.subjectApoptosisen
dc.subjectBromodeoxyuridine/pharmacokineticsen
dc.subjectCell Cycle/drug effectsen
dc.subjectCell Division/drug effectsen
dc.subjectCell Nucleus/*drug effects/metabolism/ultrastructureen
dc.subjectCell Survival/drug effectsen
dc.subjectHeLa Cellsen
dc.subjectHumansen
dc.subjectIn Situ Nick-End Labelingen
dc.subjectLaminsen
dc.subjectMicroscopy, Videoen
dc.subjectMitotic Index/drug effectsen
dc.subjectNF-kappa B/*metabolismen
dc.subjectNuclear Envelope/*drug effects/ultrastructureen
dc.subjectNuclear Proteins/metabolismen
dc.subjectPaclitaxel/*toxicityen
dc.subjectTumor Cells, Cultureden
dc.subjectTumor Necrosis Factor-alpha/drug effectsen
dc.titleTaxol affects nuclear lamina and pore complex organization and inhibits import of karyophilic proteins into the cell nucleusen
heal.abstractTreatment of human carcinoma cells with Taxol induces focal unraveling of the nuclear lamina and extensive clustering or ectopic localization of the nuclear pore complexes. These striking aberrations develop when the cells are transferred to drug-free medium and are allowed to complete mitosis. As could be confirmed by terminal deoxynucleotidyl transferase-mediated nick end labeling assays, 4,6-diamidino-2-phenylindole staining, 5-bromo-2-deoxyuridine incorporation, and examination of the nuclear lamins by Western blotting, the malformation of the nuclear envelope is not a consequence of apoptosis or G1 arrest. In fact, Taxol-treated cells possessing a defective nuclear envelope remain alive and replication-competent for at least 24 h, undergoing programmed death 72 h after removal of the drug. While still in the nonapoptotic state, these cells lose the ability to import karyophilic proteins into the nucleus. Diminished nucleocytoplasmic transport through the nuclear pore complex can be readily demonstrated by in vitro assays involving digitonin-permeabilized cells or in vivo monitoring of nuclear factor-kappaB translocation upon stimulation with tumor necrosis factor-alpha. These observations reveal novel cellular targets of antimicrotubule drugs and may pave the way for improved schemes of anticancer treatment.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/10493517-
heal.identifier.secondaryhttp://cancerres.aacrjournals.org/content/59/18/4625.full.pdf-
heal.journalNameCancer Resen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate1999-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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