Modulation of function of multidrug resistance associated-proteins by Kaempferia parviflora extracts and their components.
In this study, the effects of extracts and flavone derivatives from the rhizome of Kaempferia parviflora on multidrug resistance associated-proteins (MRP)-mediated transport in A549 cells were examined. The cells employed express MRP1 and MRP2, but not P-glycoprotein. The cellular accumulation of calcein, an MRP substrate, was significantly increased by various MRP inhibitors without being affected by verapamil, a typical P-glycoprotein inhibitor. Ethanol and aqueous extracts from K. parviflora rhizome increased the accumulation of calcein and doxorubicin in A549 cells in a concentration-dependent manner. The inhibitory potency of the ethanol extract for MRP function was greater than that of the aqueous extract. Among six flavone derivatives isolated from K. parviflora rhizome, 5,7-dimethoxyflavone exhibited a maximal stimulatory effect on the accumulation of doxorubicin in A549 cells. The accumulation of doxorubicin was increased by four flavone derivatives without 5-hydroxy group, but not by the other two flavone derivatives with 5-hydroxy group. In addition, 5,7-dimethoxyflavone and 3,5,7,3',4'-pentamethoxyflavone decreased resistance to doxorubicin in A549 cells. These findings indicate that extracts and flavone derivatives from the rhizome of K. parviflora suppress MRP function, and therefore may be useful as modulators of multidrug resistance in cancer cells.
Patanasethanont
Denpong
D
Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Nagai
Junya
J
Matsuura
Chie
C
Fukui
Kyoko
K
Sutthanut
Khaetthareeya
K
Sripanidkulchai
Bung-orn
BO
Yumoto
Ryoko
R
Takano
Mikihisa
M
D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004317:Doxorubicin / Q000633:toxicity; D000431:Ethanol / Q000737:chemistry; D047309:Flavones / Q000494:pharmacology*; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology; D027343:Rhizome / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry; D030521:Zingiberaceae / Q000737:chemistry*
D000903:Antibiotics, Antineoplastic; D004121:Dimethyl Sulfoxide; D004317:Doxorubicin; D000431:Ethanol; D047309:Flavones; D005452:Fluoresceins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010936:Plant Extracts; D012997:Solvents; D014867:Water; C007740:fluorexon