Document Detail


Inhibition of ATP-sensitive potassium channels causes reversible cell-cycle arrest of human breast cancer cells in tissue culture.
MedLine Citation:
PMID:  7822427     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this study was to determine if potassium channel activity is required for the proliferation of MCF-7 human mammary carcinoma cells. We examined the sensitivities of proliferation and progress through the cell cycle to each of nine potassium channel antagonists. Five of the potassium channel antagonists produced a concentration-dependent inhibition of cell proliferation with no evidence of cytotoxicity following a 3-day or 5-day exposure to drug. The IC50 values for these five drugs, quinidine (25 microM), glibenclamide (50 microM), linogliride (770 microM), 4-aminopyridine (1.6 mM), and tetraethylammonium (5.8 mM) were estimated from their respective concentration-response curves. Four other potassium channel blockers were tested at supra-maximal channel blocking concentrations, including charybdotoxin (200 nM), iberiotoxin (100 nM), margatoxin (10 nM), and apamin (500 nM), and they had no effect on MCF-7 cell proliferation, viability, or cell cycle distribution. Of the five drugs that inhibited proliferation, only quinidine, glibenclamide, and linogliride also affected the cell cycle distribution. Cell populations exposed to each of these drugs for 3 days showed a statistically significant accumulation in G0/G1 phase and a significant proportional reduction in S phase and G2/M phase cells. The inhibition of cell proliferation correlated significantly with the extent of cell accumulation in G0/G1 phase and the threshold concentrations for inhibition of growth and G0/G1 arrest were similar. The G0/G1 arrest produced by quinidine and glibenclamide were reversed by removing the drug, and cells released from arrest entered S phase synchronously with a lag period of approximately 24 hours. Based on the differential sensitivity of cell proliferation and cell cycle progression to the nine potassium channel antagonists, we conclude that inhibition of ATP-sensitive potassium channels in these human mammary carcinoma cells, reversibly arrests the cells in the G0/G1 phase of the cell cycle, resulting in an inhibition of cell proliferation.
Authors:
K A Woodfork; W F Wonderlin; V A Peterson; J S Strobl
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  162     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  1995 Feb 
Date Detail:
Created Date:  1995-02-16     Completed Date:  1995-02-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  163-71     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown 26506.
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MeSH Terms
Descriptor/Qualifier:
4-Aminopyridine / pharmacology
Breast Neoplasms / pathology*
Cell Cycle / drug effects*
Cell Division / drug effects
Glyburide / pharmacology
Humans
Potassium Channel Blockers*
Potassium Channels / physiology
Pyrrolidines / pharmacology
Quinidine / pharmacology
Tetraethylammonium
Tetraethylammonium Compounds / pharmacology
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA46350/CA/NCI NIH HHS; DK44769/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Potassium Channel Blockers; 0/Potassium Channels; 0/Pyrrolidines; 0/Tetraethylammonium Compounds; 10238-21-8/Glyburide; 504-24-5/4-Aminopyridine; 56-54-2/Quinidine; 66-40-0/Tetraethylammonium; 75358-37-1/linogliride

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


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