title: Modulation of P-glycoprotein-mediated resistance by kaempferol derivatives isolated from Zingiber zerumbet.
abstract: 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.
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Soo Yeon
authors.initials: SY
authors.lastname: Chung
authors.forename: Dae Sik
authors.initials: DS
authors.lastname: Jang
authors.forename: Ah-Reum
authors.initials: AR
authors.lastname: Han
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Jang
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Seo
authors.forename: Hwa Jeong
authors.initials: HJ
authors.lastname: Lee
mesh_terms: 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*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044949:Kaempferols; C006552:kaempferol; D014700:Verapamil; D003630:Daunorubicin