Document Detail

Effects of fluorinated inositols on the proliferation of Swiss 3T3 fibroblasts.
MedLine Citation:
PMID:  8318004     Owner:  NLM     Status:  MEDLINE    
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.
S C Cosulich; J Offer; G A Smith; R Hesketh; J C Metcalfe
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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    
Department of Biochemistry, University of Cambridge, U.K.
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MeSH Terms
3T3 Cells
Adenosine Diphosphate / metabolism
Adenosine Triphosphate / metabolism
Cell Division / drug effects*
DNA Replication / drug effects
Fluorine / pharmacology*
Inositol / analogs & derivatives*,  pharmacology*
Structure-Activity Relationship
Thymidine / metabolism
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

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