title: Korean red ginseng extract enhances paclitaxel distribution to mammary tumors and its oral bioavailability by P-glycoprotein inhibition.
abstract: 1. Drug efflux by P-glycoprotein (P-gp) is a common resistance mechanism of breast cancer cells to paclitaxel, the primary chemotherapy in breast cancer. As a means of overcoming the drug resistance-mediated failure of paclitaxel chemotherapy, the potential of Korean red ginseng extract (KRG) as an adjuvant chemotherapy has been reported only in in vitro. Therefore, we assessed whether KRG alters P-gp mediated paclitaxel efflux, and therefore paclitaxel efficacy in in vitro and vivo models. 2. KRG inhibited P-gp protein expression and transcellular efflux of paclitaxel in MDCK-mdr1 cells, but KRG was not a substrate of P-gp ATPase. In female rats with mammary tumor, the combination of paclitaxel with KRG showed the greater reduction of tumor volumes, lower P-gp protein expression and higher paclitaxel distribution in tumors, and greater oral bioavailability of paclitaxel than paclitaxel alone. 3. From these results, KRG increased systemic circulation of oral paclitaxel and its distribution to tumors via P-gp inhibition in rats and under the current study conditions.
authors.affiliation: a BK21 PLUS R-FIND Team and College of Pharmacy, Dongguk University-Seoul , Goyang , Republic of Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Bae
authors.affiliation: a BK21 PLUS R-FIND Team and College of Pharmacy, Dongguk University-Seoul , Goyang , Republic of Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: a BK21 PLUS R-FIND Team and College of Pharmacy, Dongguk University-Seoul , Goyang , Republic of Korea.
authors.forename: Hee-Sung
authors.initials: HS
authors.lastname: Chae
authors.affiliation: b Department of Internal Medicine , Dongguk University, Ilsan Hospital , Goyang , Republic of Korea , and.
authors.forename: Do Yeun
authors.initials: DY
authors.lastname: Kim
authors.affiliation: c Division of Endocrinology and Metabolism , Department of Internal Medicine, Dongguk University Ilsan Hospital , Koyang , Republic of Korea.
authors.forename: Han Seok
authors.initials: HS
authors.lastname: Choi
authors.affiliation: a BK21 PLUS R-FIND Team and College of Pharmacy, Dongguk University-Seoul , Goyang , Republic of Korea.
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Chin
authors.affiliation: a BK21 PLUS R-FIND Team and College of Pharmacy, Dongguk University-Seoul , Goyang , Republic of Korea.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Choi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D001943:Breast Neoplasms / Q000378:metabolism; D004285:Dogs; D005260:Female; D061985:Madin Darby Canine Kidney Cells; D017239:Paclitaxel / Q000378:metabolism*; D005894:Panax; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D010936:Plant Extracts; D017239:Paclitaxel
keywords: Bioavailability; Korean red ginseng extract; P-glycoprotein inhibition; distribution; mammary tumors; paclitaxel