Document Detail


Effects of fluorinated inositols on the proliferation of Swiss 3T3 fibroblasts.
MedLine Citation:
PMID:  8318004     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The six monodeoxyfluoro-myo-inositols (nFIns) have previously been synthesized as potential inhibitors of signalling pathways mediated by phosphoinositides and their derivatives. Each of the six nFIns isomers was introduced into Swiss 3T3 fibroblasts by the techniques of microinjection or scrape loading at intracellular concentrations of approx. 2-4 mM. Of the six nFIns analogues, only 3FIns and 5FIns inhibited the serum-stimulated proliferation of 3T3 fibroblasts assayed by cell counting. Proliferation was inhibited to a similar extent by 3FIns or 5FIns, irrespective of which technique was used to introduce the nFIns analogues into the cells. Proliferation of cells 35 h after serum stimulation (i.e. when the first cell cycle was completed in control cells) was inhibited by approx. 50% by both 3FIns and 5FIns, and entry into S phase in the first cell cycle was inhibited to the same extent. This indicated that the nFIns analogues were inhibiting proliferation in the G1 phase of the cell cycle. Proliferation during the second cell cycle (35-60 h after stimulation) was inhibited by 75-85%. The inhibitory nFIns analogues were not toxic to the cells, nor did they affect the cellular ATP/ADP ratio. The effectiveness of the nFIns analogues in inhibiting proliferation was directly correlated with their ability to be incorporated into phosphatidylinositol analogues, suggesting that they may act by modulating phosphoinositide signalling pathways or other functions essential for DNA synthesis.
Authors:
S C Cosulich; J Offer; G A Smith; R Hesketh; J C Metcalfe
Related Documents :
7918674 - Expression of annexin vi in a431 carcinoma cells suppresses proliferation: a possible r...
10386164 - Analysis of hematopoietic cell specific protein, m-dock.
6873194 - Onset of dna replication in nuclei of proliferating and resting nih 3t3 fibroblasts fol...
6086634 - Endogenous hyaluronate-cell surface interactions in 3t3 and simian virus-transformed 3t...
22617454 - High sensitivity of embryonic stem cells to proteasome inhibitors correlates with low e...
12948024 - Toward targeted oral vaccine delivery systems: selection of lectin mimetics from combin...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  292 ( Pt 3)     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1993-07-27     Completed Date:  1993-07-27     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  719-24     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, University of Cambridge, U.K.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Adenosine Diphosphate / metabolism
Adenosine Triphosphate / metabolism
Animals
Cell Division / drug effects*
DNA Replication / drug effects
Fluorine / pharmacology*
Inositol / analogs & derivatives*,  pharmacology*
Mice
Microinjections
Structure-Activity Relationship
Thymidine / metabolism
Tritium
Chemical
Reg. No./Substance:
10028-17-8/Tritium; 50-89-5/Thymidine; 56-65-5/Adenosine Triphosphate; 58-64-0/Adenosine Diphosphate; 6917-35-7/Inositol; 7782-41-4/Fluorine
Comments/Corrections

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


Previous Document:  Separation and partial characterization of proteinases with substrate specificity for basic amino ac...
Next Document:  Penicillin-binding protein 2x of Streptococcus pneumoniae: enzymic activities and interactions with ...