Document Detail


A non-characteristic response of L1210 cells to lovastatin.
MedLine Citation:
PMID:  8074684     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Isoprenylated proteins are believed to play an important role in DNA synthesis and subsequent cell cycle progression. Inhibition of the biosynthesis of these isoprenylated proteins results in a decrease in DNA synthesis and a characteristic G1 blockade of the cell cycle. This inhibition can be achieved by incubation of cells in the presence of a hydroxy-methylglutaryl-coenzyme A reductase inhibitor (lovastatin) and can be reversed by addition of exogenous mevalonate. When incubated in the presence of lovastatin, L1210 wild-type cells are not inhibited at G1 but rather progress to a G2/M blockade, which is reversible with exogenous mevalonate. Thymidine incorporation has also shown that DNA synthesis is occurring until this blockade is achieved. However, when L1210 cells resistant to cisplatin are incubated in the presence of lovastatin, the characteristic G1 cell cycle blockade and DNA synthesis inhibition occur. The understanding of this mechanism and the role that isoprenylated proteins play in the regulation of DNA synthesis and cell cycle progression may gain great insight into the abnormal control of the cancer cell.
Authors:
K J Engelke; M P Hacker
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  203     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  1994 Aug 
Date Detail:
Created Date:  1994-09-29     Completed Date:  1994-09-29     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  400-7     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Vermont, Burlington 05405.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle / drug effects*
DNA, Neoplasm / biosynthesis
G1 Phase
G2 Phase
Kinetics
Leukemia L1210 / pathology*
Lovastatin / pharmacology*
Mevalonic Acid / pharmacology*
Mice
Mitosis
Protein Prenylation
S Phase
Thymidine / metabolism
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/DNA, Neoplasm; 150-97-0/Mevalonic Acid; 50-89-5/Thymidine; 75330-75-5/Lovastatin

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


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