Linked Life Data

8631019

Source:http://linkedlifedata.com/resource/pubmed/id/8631019

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1996-7-3
pubmed:abstractText
Paclitaxel at low concentrations (10 nM for 20 h) induces approximately 90% mitotic block at the metaphase/anaphase transition in HeLa cells, apparently by suppressing dynamics of spindle microtubules (M. A. Jordan et al., Proc. Natl. Acad. Sci. USA, 90: 9552-9556, 1993). It is not known, however, whether inhibition of mitosis by such low paclitaxel concentrations results in cell death. In the present work, we found that after removal of paclitaxel (10 nM-1 microM), blocked cells did not resume proliferation. Instead, cells exited mitosis abnormally within 24 h. They did not progress through anaphase or cytokinesis but entered an interphase-like state (chromatin decondensed, and an interphase-like microtubule array and nuclear membranes reformed). Many cells (> or = 55%) contained multiple nuclei. Additional DNA synthesis and polyploidy did not occur. DNA degradation into nucleosome-sized fragments characteristic of apoptosis began during drug incubation and increased after drug removal. Cells died within 48-72 h. Incubation with paclitaxel (10 nM for 20 h) resulted in high intracellular drug accumulation (8.3 microM) and little efflux after paclitaxel removal; intracellular retention of paclitaxel may contribute to its efficacy. The results support the hypothesis that the most potent chemotherapeutic mechanism of paclitaxel is kinetic stabilization of spindle microtubule dynamics.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
816-25
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death.
pubmed:affiliation
Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara 93106, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.