Document Detail


Effect of combination of suboptimal concentrations of P-glycoprotein blockers on the proliferation of MDR1 gene expressing cells.
MedLine Citation:
PMID:  8575863     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pharmacologically active in vivo doses of P-glycoprotein (Pgp) blockers, specifically verapamil, Cremophor EL and PSC833 cause toxicity in addition to that from the concomitantly used cancer chemotherapeutic drugs. It was shown before that these blockers cause different types of toxicities in vivo. We found that these 3 chemically distinct Pgp blockers exert different biophysical effects on the membranes of L1210 MDR cells. They also affect the general metabolism of these cells differently, but all block affinity labeling of Pgp. We could also show that the combination of suboptimal doses of these blockers can restore the uptake of the Pgp substrate rhodamine 123 into L1210MDR, 3T3MDR and KB-VI cells and can reduce the survival rate of these cells when treated in combination with daunorubicin. Our results suggest that the combination of suboptimal doses of these Pgp blockers may be advantageous in clinical practice.
Authors:
M Hwang; C H Ahn; P S Pine; J J Yin; C A Hrycyna; T Licht; A Aszalos
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  65     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  1996 Jan 
Date Detail:
Created Date:  1996-03-13     Completed Date:  1996-03-13     Revised Date:  2007-07-24    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  389-97     Citation Subset:  IM    
Affiliation:
Center for Drug Evaluation and Research, Food and Drug Administration, Washington, DC 20204, USA.
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MeSH Terms
Descriptor/Qualifier:
Calcium Channel Blockers / pharmacology*
Cell Division / drug effects
Cell Membrane / drug effects,  metabolism*
Cyclosporins / pharmacology*
Glycerol / analogs & derivatives*,  pharmacology
Humans
Leukemia
P-Glycoprotein / antagonists & inhibitors*,  genetics*
Transfection
Tumor Cells, Cultured
Verapamil / pharmacology*
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Cyclosporins; 0/P-Glycoprotein; 121584-18-7/valspodar; 52-53-9/Verapamil; 56-81-5/Glycerol; 63393-92-0/cremophor EL

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


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