期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 600, 期 1-3, 页码 45-49出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2008.10.025
关键词
P-glycoprotein; ABCB1; MRP1; ABC transporter; Multidrug resistance; Citrus phytochemical
资金
- Encouragement of Young Scientists from the Ministry of Education, Culture, Sports, Science and Technology of Japan
- Mitsui Sumitomo Insurance Welfare Foundation (T.N.)
- Promotion and Mutual Aid Corporation for Private Schools in Japan
The effects of dietary chemopreventive citrus phytochemicals on the drug efflux transporters P-glycoprotein (ABCB1) and multidrug resistance protein 1 (MRP1, ABCC1) were investigated using P-glycoprotein-overexpressing human carcinoma KB-C2 cells and human MRP1 gene-transfected KB/MRP cells. The effects of natural chemopreventive citrus phytochemicals, such as auraptene, nobiletin, citral, citronellal, limonene, limonin, and synephrine were examined. The accumulation of daunorubicin, a fluorescent substrate of P-glycoprotein, increased in the presence of auraptene and nobiletin in KB-C2 cells. Nobiletin also increased the accumulation of calcein, a fluorescent substrate of MRP1, in KB/MRP cells. The ATPase activity of P-glycoprotein was stimulated by auraptene and nobiletin. The ATPase activity of MRP1 was stimulated by nobiletin. These results suggest that chemopreventive citrus phytochemicals, such as nobiletin found in oranges, have inhibitory effects on P-glycoprotein and/or MRP1, and may cause food-drug interactions. (c) 2008 Elsevier B.V. All rights reserved.
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