Document Detail


Inhibition of P-glycoprotein-dependent multidrug resistance by an isoquinolinesulfonamide compound H-87 in rat ascites hepatoma AH66 cells.
MedLine Citation:
PMID:  8799494     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of an isoquinolinesulfonamide compound, H-87, on naturally acquired multidrug-resistance (MDR) in rat hepatoma AH66 cells were examined. AH66 cells were highly resistant to vinblastine, SN-38, an active camptothecin analog, adriamycin, and etoposide, compared with the sensitive variant AH66F cells. Although H-87 hardly affected the sensitivities to antitumor agents of AH66F cells, this compound completely inhibited the resistance to vinblastine, moderately inhibited the resistance to SN-38 and adriamycin and had little effect on etoposide, mitomycin C, cisplatin, and 5-fluorouracil. H-87 significantly decreased the efflux of vinblastine from the resistant cells and increased the drug accumulation. SN-38 and adriamycin also exhibited a weak but significant increase in vinblastine accumulation in AH66 cells. H-87 inhibited [3H]azidopine-photolabeling to 160 kDa P-glycoprotein in the plasma membrane of AH66 cells, as reported in acquired MDR leukemic cells. Consequently, the MDR-overcoming effect of H-87 seems to be due to its direct inhibition of the binding of antitumor agents on P-glycoprotein in the plasma membrane.
Authors:
S Nakamura; T Minamino; M Nomura; S Wakusawa; K Miyamoto; H Hidaka
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  19     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  1996 Jun 
Date Detail:
Created Date:  1997-01-02     Completed Date:  1997-01-02     Revised Date:  2007-09-25    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  886-9     Citation Subset:  IM    
Affiliation:
Fujiyakuhin Co., Ltd., Ohmiya, Japan.
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MeSH Terms
Descriptor/Qualifier:
Affinity Labels
Animals
Antineoplastic Agents / pharmacology
Azides / metabolism
Camptothecin / analogs & derivatives,  pharmacology
Dihydropyridines / metabolism
Doxorubicin / pharmacology
Drug Resistance, Multiple*
Drug Resistance, Neoplasm*
Etoposide / pharmacology
Female
Isoquinolines / pharmacology*
P-Glycoprotein / antagonists & inhibitors
Protein Binding / drug effects
Protein Kinase Inhibitors
Rats
Sulfonamides*
Tritium
Tumor Cells, Cultured
Vinblastine / pharmacology
Chemical
Reg. No./Substance:
0/Affinity Labels; 0/Antineoplastic Agents; 0/Azides; 0/Dihydropyridines; 0/Isoquinolines; 0/P-Glycoprotein; 0/Protein Kinase Inhibitors; 0/Sulfonamides; 10028-17-8/Tritium; 100286-90-6/irinotecan; 127243-85-0/H 89; 23214-92-8/Doxorubicin; 33419-42-0/Etoposide; 7689-03-4/Camptothecin; 865-21-4/Vinblastine; 90523-31-2/azidopine

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


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