Document Detail


Paclitaxel induces primary and postmitotic G1 arrest in human arterial smooth muscle cells.
MedLine Citation:
PMID:  15254417     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Paclitaxel (PTX), a microtubule-active drug, causes mitotic arrest leading to apoptosis in certain tumor cell lines. Here we investigated the effects of PTX on human arterial smooth muscle cell (SMC) cells. In SMC, PTX caused both (a) primary arrest in G(1) and (b) post-mitotic arrest in G(1). Post-mitotic cells were multinucleated (MN) with either 2C (near-diploid) or 4C (tetraploid) DNA content. At PTX concentrations above 12 ng/ml, MN cells had 4C DNA content consistent with the lack of cytokinesis during abortive mitosis. Treatment with 6-12 ng/ml PTX yielded MN cells with 2C DNA content. Finally, 1-6 ng/ml of PTX, the lowest concentrations that affected cell proliferation, caused G(1) arrest without multinucleation. It is important that PTX did not cause apoptosis in SMC. The absence of apoptosis could be explained by mitotic exit and G(1) arrest as well as by low constitutive levels of caspase expression and by p53 and p21 induction. Thus, following transient mitotic arrest, SMC exit mitosis to form MN cells. These post-mitotic cells were subsequently arrested in G(1) but maintained normal elongated morphology and were viable for at least 21 days. We conclude that in SMC PTX causes post-mitotic cell cycle arrest rather than cell death.
Authors:
Mikhail V Blagosklonny; Zbigniew Darzynkiewicz; H Dorota Halicka; Piotr Pozarowski; Zoya N Demidenko; James J Barry; Kalpana R Kamath; Robert A Herrmann
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Publication Detail:
Type:  Journal Article     Date:  2004-08-24
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  3     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-10-19     Completed Date:  2005-10-04     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1050-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aorta / cytology
Apoptosis / drug effects
Cell Count
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects,  physiology
Coronary Vessels / cytology
G1 Phase / drug effects*
HL-60 Cells / chemistry,  metabolism,  pathology
Humans
Jurkat Cells / chemistry,  metabolism,  pathology
Mitosis / drug effects
Muscle, Smooth, Vascular / cytology*,  drug effects
Myocytes, Smooth Muscle / drug effects*
Paclitaxel / pharmacology*
Ploidies
Proto-Oncogene Proteins p21(ras) / metabolism
Grant Support
ID/Acronym/Agency:
R01 CA028704/CA/NCI NIH HHS; R01 CA028704-26/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
33069-62-4/Paclitaxel; EC 3.6.5.2/HRAS protein, human; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras)

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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