Document Detail


Inhibitory effects of ginsenosides and their hydrolyzed metabolites on daunorubicin transport in KB-C2 cells.
MedLine Citation:
PMID:  17917277     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We studied the effects of ginsenosides and their metabolites on daunorubicin transport in multidrug-resistant P-glycoprotein (P-gp)-overexpressing KB-C2 cells. Ginsenoside Rg1, which is a protopanaxatriol-type ginseng saponin, did not have any effects on the accumulation of P-gp substrate daunorubicin. On the other hand, its metabolite M4, which has no sugar moiety, increased the accumulation 3.6-fold at 5 microM. Metabolites of protoanaxadiol-type saponin M1 and M12 also increased accumulation, but the effects were less than that of M4. The findings showed larger effects of metabolites without glucose moieties. Analysis of verapamil-stimulated ATPase activity in membrane vesicles expressing human P-gp suggested that the increased daunorubicin accumulation by M4 was at least partly due to ATPase inhibition of P-gp.
Authors:
Shuji Kitagawa; Tomoharu Takahashi; Tomohiro Nabekura; Eiichi Tachikawa; Hideo Hasegawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  30     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-05     Completed Date:  2007-11-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1979-81     Citation Subset:  IM    
Affiliation:
Kobe Pharmaceutical University, Kobe, Japan. kitagawa@niigata-pharm.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphatases / metabolism
Antibiotics, Antineoplastic / metabolism*
Biological Transport, Active / drug effects
Calcium Channel Blockers / pharmacology
Cell Membrane / drug effects,  enzymology
Colchicine / pharmacology
Cyclosporine / pharmacology
Daunorubicin / metabolism*
Drug Resistance, Neoplasm / drug effects
Ginsenosides / chemistry,  pharmacokinetics*,  pharmacology*
Humans
Hydrolysis
KB Cells
Multidrug Resistance-Associated Proteins / genetics
P-Glycoprotein / biosynthesis,  genetics,  physiology
Structure-Activity Relationship
Triterpenes / pharmacology
Verapamil / pharmacology
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Calcium Channel Blockers; 0/Ginsenosides; 0/Multidrug Resistance-Associated Proteins; 0/P-Glycoprotein; 0/Triterpenes; 0/multidrug resistance-associated protein 1; 20830-81-3/Daunorubicin; 52-53-9/Verapamil; 545-22-2/dammarane; 59865-13-3/Cyclosporine; 64-86-8/Colchicine; EC 3.6.1.-/Adenosine Triphosphatases

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


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