Modulation of P-glycoprotein-mediated resistance by kaempferol derivatives isolated from Zingiber zerumbet.
This study examined the effects of the kaempferol derivatives extracted from Zingiber zerumbet on the accumulation and efflux of [(3)H]-daunomycin (DNM) in P-glycoprotein (P-gp) overexpressing multidrug resistant (MDR) human breast cancer cells, MCF-7/ADR. Of six kaempferol derivatives extracted from Z. zerumbet, kaempferol-3-O-methyl ether (1) and kaempferol-3,4'-O-dimethyl ether (2) showed a potent P-gp inhibitory effect as great as verapamil, a well-known P-gp inhibitor. The P-gp inhibitory activity of these two compounds was through a 3-fold increase of the level of [(3)H]-DNM accumulation and a decrease of P-gp-mediated efflux. These results suggest that the kaempferol derivative components of Z. zerumbet can be used as a scaffold for developing agents that reverse P-gp-mediated MDR in human cancer chemotherapy.
Chung
Soo Yeon
SY
College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
Jang
Dae Sik
DS
Han
Ah-Reum
AR
Jang
Jung Ok
JO
Kwon
Youngjoo
Y
Seo
Eun-Kyoung
EK
Lee
Hwa Jeong
HJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D044949:Kaempferols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D014700:Verapamil / Q000494:pharmacology; D030521:Zingiberaceae / Q000737:chemistry*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044949:Kaempferols; C006552:kaempferol; D014700:Verapamil; D003630:Daunorubicin