Inhibitory effects of ginsenosides and their hydrolyzed metabolites on daunorubicin transport in KB-C2 cells.
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.
Kitagawa
Shuji
S
Kobe Pharmaceutical University, Kobe, Japan. kitagawa@niigata-pharm.ac.jp
Takahashi
Tomoharu
T
Nabekura
Tomohiro
T
Tachikawa
Eiichi
E
Hasegawa
Hideo
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D003078:Colchicine / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003630:Daunorubicin / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D036145:Ginsenosides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007624:KB Cells; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D000097669:Dammaranes
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000251:Adenosine Triphosphatases; D000903:Antibiotics, Antineoplastic; D002121:Calcium Channel Blockers; D003078:Colchicine; D016572:Cyclosporine; D003630:Daunorubicin; D036145:Ginsenosides; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014315:Triterpenes; D014700:Verapamil; D000097669:Dammaranes; C421109:multidrug resistance-associated protein 1