Document Detail


A nuclear budding mechanism in transiently arrested cells generates drug-sensitive and drug-resistant cells.
MedLine Citation:
PMID:  19464429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HCT116 (p53(+/+)) human colon carcinoma cells treated with nanomolar concentrations of doxorubicin underwent transient senescence, synthesized DNA, showed endopolyploidization, increased their size and became multinucleated without a significant increase in mitosis. Nuclei underwent a budding process that involved the release of buds outside the nuclear membrane, and some of the buds seemed to escape from the polyploid cells. A clonogenic assay showed that some cells proliferated following the initial treatment. In general, cells ensuing after budding were not resistant to a variety of drugs, although some of them turned out to be resistant, indicating a potential selective advantage. Nuclear budding was accompanied by changes in protein levels in the giant cells, including inhibition of p53 and enhanced expression of p21(WAF1) and the meiosis-related Mos. The buds might be a mechanism for the segregation and elimination of redundant DNA, or for generating viable aneuploid cells with a potentially extended life span.
Authors:
Sylvia Mansilla; Marc Bataller; José Portugal
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-05
Journal Detail:
Title:  Biochemical pharmacology     Volume:  78     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-05-25     Completed Date:  2009-06-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  123-32     Citation Subset:  IM    
Affiliation:
Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientific de Barcelona, Baldiri Reixach 10, E-08028 Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects,  physiology
Cell Aging / drug effects,  physiology
Cell Cycle / drug effects,  physiology
Cell Nucleus / drug effects,  physiology*
Cell Nucleus Division / drug effects,  physiology*
Cell Proliferation / drug effects
Doxorubicin / pharmacology
Drug Resistance, Multiple / drug effects,  physiology
Drug Resistance, Neoplasm / drug effects,  physiology*
HCT116 Cells
Humans
Chemical
Reg. No./Substance:
23214-92-8/Doxorubicin

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


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