Document Detail


Effects of amiloride analogues on human erythroleukemic K562 cell growth and on induction of hemoglobin synthesis by adriamycin.
MedLine Citation:
PMID:  2379546     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Treatment with adriamycin for 8-14 h irreversibly induces K562 human erythroleukemic cells to synthesize hemoglobin. With 16-h exposure, this effect is maximal at concentrations between 180 and 400 nM, yielding 70%-90% benzidine-positive (B+) cells and 24 pg/cell hemoglobin 4 days after the beginning of adriamycin treatment. This induction is accompanied by changes in ouabain-sensitive 86Rb influx opposite to those seen with murine erythroleukemic (MEL) cells. Amiloride and several amiloride analogues strongly inhibit adriamycin induction of hemoglobin synthesis as well as cell growth in the absence of adriamycin. The inhibition of induction is enhanced with the analogues bearing a benzyl or substituted benzyl group on the 5-amino or on a terminal guanidino nitrogen atom. The effect on growth was somewhat greater with the analogue bearing a 2-chlorobenzyl moiety on a terminal guanidino nitrogen atom and with the one bearing a 2-fluorobenzyl group on the 5-amino nitrogen atom. The structural features required for growth inhibition resemble those seen with MEL cells, but the features required for inhibition of induction of hemoglobin synthesis are completely different. These data suggest that different specific binding sites are involved in these two effects of amiloride and its analogues.
Authors:
R C Steinfeld; M C Severski; E J Cragoe; P A Knauf
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental hematology     Volume:  18     ISSN:  0301-472X     ISO Abbreviation:  Exp. Hematol.     Publication Date:  1990 Aug 
Date Detail:
Created Date:  1990-09-07     Completed Date:  1990-09-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  818-23     Citation Subset:  IM    
Affiliation:
Department of Biophysics, University of Rochester School of Medicine and Dentistry, New York 14642.
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MeSH Terms
Descriptor/Qualifier:
Amiloride / analogs & derivatives,  pharmacology*
Biological Transport / drug effects
Cell Division / drug effects
Dose-Response Relationship, Drug
Doxorubicin / biosynthesis
Hematopoiesis / drug effects*
Hemoglobins / biosynthesis*
Humans
Leukemia, Erythroblastic, Acute / pathology
Potassium / physiology
Structure-Activity Relationship
Time Factors
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
DK27495/DK/NIDDK NIH HHS; T32 HL07152/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hemoglobins; 23214-92-8/Doxorubicin; 2609-46-3/Amiloride; 7440-09-7/Potassium

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


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