title: Effects of plant sterols on human multidrug transporters ABCB1 and ABCC1.
abstract: The effects of dietary plant sterols on human drug efflux transporters P-glycoprotein (P-gp, ABCB1) and multidrug resistance protein 1 (MRP1, ABCC1) were investigated using P-gp-overexpressing human carcinoma KB-C2 cells and human MRP1 gene-transfected KB/MRP cells. The effects of natural phytosterols found in foods, herbs, and dietary supplements such as beta-sitosterol, campesterol, stigmasterol, fucosterol, and z-guggulsterone were investigated. The accumulation of daunorubicin or rhodamine 123, fluorescent substrates of P-gp, increased in the presence of guggulsterone in KB-C2 cells. The efflux of rhodamine 123 from KB-C2 cells was inhibited by guggulsterone. Guggulsterone also increased the accumulation of calcein, a fluorescent substrate of MRP1, in KB/MRP cells. The ATPase activities of P-gp and MRP1 were stimulated by guggulsterone. These results suggest that guggulsterone, a natural dietary hypolipidemic agent have dual inhibitory effects on P-gp and MRP1 and the potencies to cause food-drug interactions.
authors.affiliation: Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashi-jima, Akiha-ku, Niigata 956-8603, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nabekura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamaki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ueno
authors.forename: Shuji
authors.initials: S
authors.lastname: Kitagawa
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D010840:Phytosterols / Q000008:administration & dosage*; D011282:Pregnenediones / Q000008:administration & dosage*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010840:Phytosterols; D011282:Pregnenediones; C513055:ABCB1 protein, human; C023617:pregna-4,17-diene-3,16-dione; C421109:multidrug resistance-associated protein 1