Effects of Dietary Ingredients on Function and Expression of P-Glycoprotein in Human Intestinal Epithelial Cells
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概要
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The present study was conducted to investigate the functional and transcriptional modulation of P-glycoprotein (MDR-1) by several dietary ingredients (piperine, capsaicin, daidzein, genistein, sesamin, curcumin, taurine) in vinblastine-resistant colon carcinoma LS-180 cells (LS-180V cells). The amount of rhodamine 123 accumulated in LS-180V cells was significantly increased by capsaicin, piperine and sesamin, whereas it was significantly reduced by daidzein and genistein which stimulated the efflux of rhodamine 123. These results suggest that the P-glycoprotein-mediated efflux is inhibited by piperine, capsaicin and sesamin and stimulated by daidzein and genistein. The concurrent addition of piperine and capsaicin seemed to inhibit synergistically the P-glycoprotein-mediated efflux. Pretreatment with sesamin for 48 h caused a significant increase in MDR1 mRNA expression without a significant effect on the expression of P-glycoprotein or accumulation of rhodamine 123. Similar pretreatment with other ingredients had little effect on the expression of MDR1 mRNA or P-glycoprotein, suggesting that they do not cause transcriptional modulation of P-glycoprotein. Piperine, genistein and curcumin have been suggested to stimulate P-glycoprotein-mediated efflux without increasing P-glycoprotein expression. In LS-180V cells, significant increases in mRNA levels of multi-drug resistance associated protein 1 (MRP1) or MRP3 were observed on pretreatment with capsaicin, daidzein, piperine and sesamin. In conclusion, our results suggest that P-glycoprotein-mediated efflux is significantly affected by dietary ingredients. Also, capsaicin, daidzein, piperine and sesamin increased significantly the mRNA expression of MRP1 or MRP3. Thus, the present study provides further evidence that repeated exposure to dietary ingredients can cause drug–food interactions by affecting the function and mRNA expression of intestinal transporters such as P-glycoprotein.
著者
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Umegaki Keizo
The National Institute Of Health And Nutrition
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YAMADA Shizuo
Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, S
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SHINOZUKA Kazumasa
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University
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OKURA Takashi
Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) and Clinic
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Shinozuka Kazumasa
Department Of Pharmacology Faculty Of Pharmaceutical Science Mukogawa Women's University
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Yamada Shizuo
Department Of Biophamacy School Of Pharmaceutical Sciences University Of Shizuoka
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Umegaki Keizo
Center of Information, National Institute of Health and Nutrition
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Ibe Michiko
Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE), School of
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Yamada Shizuo
Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE), School of Pharmaceutical Sciences, University of Shizuoka
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Okura Takashi
Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE), School of Pharmaceutical Sciences, University of Shizuoka
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Ibe Michiko
Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE), School of Pharmaceutical Sciences, University of Shizuoka
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Shinozuka Kazumasa
Department of Applied Chemistry, Faculty of Engineering, Yokohama National University
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