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.