title: Guggulsterone regulates the function and expression of P-glycoprotein in rat brain microvessel endothelial cells.
abstract: Our previous studies found that guggulsterone could inhibit P-glycoprotein-mediated multidrug resistance in P-glycoprotein over-expressed human cancer cell lines. However, the effects of guggulsterone on the ;P-glycoprotein function and expression in rat brain microvessel endothelial cells (rBMECs) are poorly understood. In the present study, we investigated whether guggulsterone has a modulative effect on the function and expression of P-glycoprotein in rBMECs. rhodamine 123 acts as a good substrate for P-glycoprotein, and agents that block P-glycoprotein have been found to increase the retention of rhodamine in cells. The results showed that the accumulation of rhodamine 123 in rBMECs was potentiated in a time-dependent manner after incubation with 30, 100 μM guggulsterone (P<0.05). Efflux of intracellular rhodamine 123 was decreased in a time-dependent manner from after 30, 100 μM guggulsterone treatment. The inhibitory effect of guggulsterone on P-glycoprotein function was reversible and remained at 120 min after removal of 30, 100 μM guggulsterone from the medium. Further results showed that guggulsterone (30, 100 μM) down-regulated the expression of P-glycoprotein, and had no influence on the expression of breast cancer resistance protein in rBMECs. In addition, the present study revealed that guggulsterone promoted the activity of P-glycoprotein ATPase in a dose-dependent manner. These results indicated that guggulsterone suppressed the function and expression of P-glycoprotein in rBMECs primary cultures.
authors.affiliation: Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Xian-Zhen
authors.initials: XZ
authors.lastname: Chen
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Xu
authors.forename: Lu-Zhong
authors.initials: LZ
authors.lastname: Xu
authors.forename: Xia-Ping
authors.initials: XP
authors.lastname: Mao
authors.forename: Ling
authors.initials: L
authors.lastname: Li
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D055806:Microvessels / Q000166:cytology*; D011282:Pregnenediones / Q000494:pharmacology*; D051381:Rats
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011282:Pregnenediones; C023617:pregna-4,17-diene-3,16-dione; D000251:Adenosine Triphosphatases
keywords: Guggulsterone; P-glycoprotein; Rat brain microvessel endothelial cell