Substrate Specificity of Aglaia loheri Active Isolate towards P-glycoprotein in Multidrug-Resistant Cancer Cells

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000388251200015&DestLinkType=FullRecord&DestApp=WOS_CPL
eISSN
1555-9475
Externe Identifier
  • Clarivate Analytics Document Solution ID: EC6MU
  • PubMed Identifier: 30475507
ISSN
1934-578X
Ausgabe der Veröffentlichung
11
Zeitschrift
NATURAL PRODUCT COMMUNICATIONS
Schlüsselwörter
  • ATP-binding cassette (ABC) transporter
  • Cancer
  • Maldi 531.2[M+H](+)
  • Meliaceae
  • Multidrug resistance
  • Phytotherapy
Paginierung
1683 - 1688
Datum der Veröffentlichung
2016
Status
Published
Titel
Substrate Specificity of <i>Aglaia loheri</i> Active Isolate towards P-glycoprotein in Multidrug-Resistant Cancer Cells
Sub types
  • Article
Ausgabe der Zeitschrift
11

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
Multidrug resistance (MDR) is a major contributory factor in the failure of chemotherapy. Concrete interpretation of P-glycoprotein (P-gp) substrate specificity, whether a substance is a substrate or an inhibitor, represents an important feature of a compound's pharmaceutical profiling in drug design and development. In this work, the P-gp substrate specificity of Maldi 531.2[M+H](+), a phenol ester from Aglaia loheri Blanco leaves was investigated. This study focuses on the effect of Maldi 531.2[M+H](+) on P-gp ATPase activity, which was examined by measuring the amount of inorganic phosphates (Pi) released as a result of ATP hydrolysis. To test the effects of Maldi 531.2[M+H](+) on MDR activity, an attempt to combine Maldi 531.2[M+H](+) with a potent P-gp substrate such as verapamil was performed. As a result of this combination treatment, two distinct patterns of interaction with P-gp activity were determined by a calcein-acetoxymethyl ester (AM) assay. Depending on the concentratgion, both stimulation and inhibition of MDR activity were observed at certain drug concentrations suggesting biphasic reactions, which can be understood as cooperative stimulation and competitive inhibition, respectively. Verapamil is a strong substrate to P-gp. Substrate specificity of Maldi 531.2[M+H](+) may be less than the substrate specificity of verapamil, but it acts additively together with low concentrations of verapamil in stimulating ATPase activity. On the one hand, verapamil and Maldi 531.2[M+H](+) exerted cooperative stimulation on P-gp. On the other hand, Maldi 531.2[M+H](+) acts as competitive inhibitor at higher concentrations.
Autoren
eISSN
1555-9475
Externe Identifier
  • PubMed Identifier: 30475507
Open access
false
ISSN
1934-578X
Ausgabe der Veröffentlichung
11
Zeitschrift
Natural product communications
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Aglaia
  • Leukemia
  • Antineoplastic Agents, Phytogenic
  • Inhibitory Concentration 50
  • Gene Expression Regulation, Neoplastic
  • Substrate Specificity
  • Drug Resistance, Neoplasm
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
Sprache
eng
Medium
Print
Paginierung
1683 - 1688
Datum der Veröffentlichung
2016
Status
Published
Datum der Datenerfassung
2018
Titel
Substrate Specificity of Aglaia loheri Active Isolate towards P-glycoprotein in Multidrug-Resistant Cancer Cells.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
11

Data source: Europe PubMed Central

Abstract
Multidrug resistance (MDR) is a major contributory factor in the failure of chemotherapy. Concrete interpretation of P-glycoprotein (P-gp) substrate specificity, whether a substance is a substrate or an inhibitor, represents an important feature of a compound's pharmaceutical profiling in drug design and development. In this work, the P-gp substrate specificity of Maldi 531.2[M+H](+), a phenol ester from Aglaia loheri Blanco leaves was investigated. This study focuses on the effect of Maldi 531.2[M+H](+) on P-gp ATPase activity, which was examined by measuring the amount of inorganic phosphates (Pi) released as a result of ATP hydrolysis. To test the effects of Maldi 531.2[M+H](+) on MDR activity, an attempt to combine Maldi 531.2[M+H](+) with a potent P-gp substrate such as verapamil was performed. As a result of this combination treatment, two distinct patterns of interaction with P-gp activity were determined by a calcein-acetoxymethyl ester (AM) assay. Depending on the concentratgion, both stimulation and inhibition of MDR activity were observed at certain drug concentrations suggesting biphasic reactions, which can be understood as cooperative stimulation and competitive inhibition, respectively. Verapamil is a strong substrate to P-gp. Substrate specificity of Maldi 531.2[M+H](+) may be less than the substrate specificity of verapamil, but it acts additively together with low concentrations of verapamil in stimulating ATPase activity. On the one hand, verapamil and Maldi 531.2[M+H](+) exerted cooperative stimulation on P-gp. On the other hand, Maldi 531.2[M+H](+) acts as competitive inhibitor at higher concentrations.
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/30475507
ISSN
1934-578X
Ausgabe der Veröffentlichung
11
Zeitschrift
Nat Prod Commun
Schlüsselwörter
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Aglaia
  • Antineoplastic Agents, Phytogenic
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitory Concentration 50
  • Leukemia
  • Substrate Specificity
Sprache
eng
Country
United States
Paginierung
1683 - 1688
Datum der Veröffentlichung
2016
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2018
Titel
Substrate Specificity of Aglaia loheri Active Isolate towards P-glycoprotein in Multidrug-Resistant Cancer Cells.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
11

Data source: PubMed

Beziehungen:
Property of

Tools