| Inhibitory effects of terpenoids on multidrug resistance-associated protein 2- and breast cancer resistance protein-mediated transport. | |
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MedLine Citation:
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PMID: 18436619 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The possibility of interactions between natural products/supplements and conventional prescription medicines is one of the most important issues in pharmacotherapeutic safety. Recently, we reported that some terpenoids such as (R)-(+)-citronellal and glycyrrhetic acid, which are present in herbal medicines, can act as inhibitors of P-glycoprotein (MDR1/ABCB1). In the present study, the effects of seven terpenoids on multidrug resistance-associated protein 2 (MRP2/ABCC2) and breast cancer resistance protein (BCRP/ABCG2)-mediated transport were investigated in vitro. Membrane vesicles were prepared from MRP2 cDNA transfected Sf9 cells derived from pupal ovarian tissue of Spodoptera frugiperda, a fall armyworm, and BCRP cDNA transfected LLC-PK1 cells derived from porcine kidney. MRP2- or BCRP-mediated efflux transport was measured as ATP-dependent accumulation of [(3)H]estradiol 17-beta-d-glucuronide (E(2)17betaG) into membrane vesicles collected by a rapid filtration technique. The effects of (R)-(+)-citronellal, (S)-(-)-beta-citronellol, alpha-terpinene, terpinolene, (-)-beta-pinene, abietic acid, and glycyrrhetic acid on the intravesicular accumulation of [(3)H]E(2)17betaG were examined. Large decreases in the [(3)H]E(2)17betaG accumulation into vesicles from MRP2-overexpressing Sf9 cells were observed in the presence of glycyrrhetic acid and abietic acid, and their IC(50) values were about 20 and 51 microM, respectively. [(3)H]E(2)17betaG accumulation into vesicles from BCRP-overexpressing LLC-PK1 cells was suppressed by only glycyrrhetic acid, with an IC(50) value of about 39 microM. Other terpenoids used in this study did not alter the ATP-dependent accumulation of [(3)H]E(2)17betaG. These findings suggest that glycyrrhetic acid and abietic acid can potently inhibit MRP2- or BCRP-mediated membrane transport and may interact with their substrates in pharmacokinetic processes. |
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Authors:
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Naoko Yoshida; Tappei Takada; Yoshikazu Yamamura; Isao Adachi; Hiroshi Suzuki; Junichi Kawakami |
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Publication Detail:
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Type: Journal Article Date: 2008-04-24 |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: 36 ISSN: 1521-009X ISO Abbreviation: Drug Metab. Dispos. Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-06-20 Completed Date: 2008-08-11 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: United States |
Other Details:
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Languages: eng Pagination: 1206-11 Citation Subset: IM |
Affiliation:
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Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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antagonists & inhibitors*,
genetics Animals LLC-PK1 Cells Multidrug Resistance-Associated Proteins / antagonists & inhibitors*, genetics Neoplasm Proteins / antagonists & inhibitors*, genetics Spodoptera Swine Terpenes / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/ABCG2 protein, human; 0/ATP-Binding Cassette Transporters; 0/Multidrug Resistance-Associated Proteins; 0/Neoplasm Proteins; 0/Terpenes; 0/multidrug resistance-associated protein 2 |
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