RRC ID 30487
Author Sheu MJ, Teng YN, Chen YY, Hung CC.
Title The functional influences of common ABCB1 genetic variants on the inhibition of P-glycoprotein by Antrodia cinnamomea extracts.
Journal PLoS One
Abstract Antrodia cinnamomea is a traditional healthy food that has been demonstrated to possess anti-inflammatory, antioxidative, and anticacer effects. The purpose of this study was to evaluate whether the ethanolic extract of A. cinnamomea (EEAC) can affect the efflux function of P-glycoprotein (P-gp) and the effect of ABCB1 genetic variants on the interaction between EEAC and P-gp. To investigate the mechanism of this interaction, Flp-In™-293 cells stably transfected with various genotypes of human P-gp were established and the expression of P-gp was confirmed by Western blot. The results of the rhodamine 123 efflux assay demonstrated that EEAC efficiently inhibited wild-type P-gp function at an IC50 concentration of 1.51 ± 0.08 µg/mL through non-competitive inhibition. The IC50 concentrations for variant-type 1236T-2677T-3435T P-gp and variant-type 1236T-2677A-3435T P-gp were 5.56 ± 0.49 µg/mL and 3.33±0.67 µg/mL, respectively. In addition, the inhibition kinetics of EEAC also changed to uncompetitive inhibition in variant-type 1236T-2677A-3435T P-gp. The ATPase assay revealed that EEAC was an ATPase stimulator and was capable of reducing verapamil-induced ATPase levels. These results indicate that EEAC may be a potent P-gp inhibitor and higher dosages may be required in subjects carrying variant-types P-gp. Further studies are required to translate this basic knowledge into clinical applications.
Volume 9(2)
Pages e89622
Published 2014-1-1
DOI 10.1371/journal.pone.0089622
PII PONE-D-13-43939
PMID 24586917
PMC PMC3934917
MeSH ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors ATP Binding Cassette Transporter, Subfamily B / genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors* ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics* ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism Adenosine Triphosphatases / metabolism Antrodia / chemistry* Genetic Variation HEK293 Cells Humans Plant Extracts / pharmacology* RNA, Messenger / genetics RNA, Messenger / metabolism Rhodamine 123 / metabolism
IF 2.74
Times Cited 11
DNA material Human MDR1 cDNA (RDB01372)