Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR)
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Mohamed EM Saeed
- Nuha Mahmoud
- Yoshikazu Sugimoto
- Thomas Efferth
- Heba Abdel-Aziz
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000432302800001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3389/fphar.2018.00481
- Externe Identifier
- Clarivate Analytics Document Solution ID: GF9MT
- PubMed Identifier: 29867487
- ISSN
- 1663-9812
- Zeitschrift
- FRONTIERS IN PHARMACOLOGY
- Schlüsselwörter
- bioinformatics
- cancer
- drug resistance
- microarray
- pharmacogenomics
- phytotherapy
- triterpene
- autocrine motility factor receptor (AMFR)
- Artikelnummer
- ARTN 481
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Titel
- Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR)
- Sub types
- Article
- Ausgabe der Zeitschrift
- 9
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Mohamed EM Saeed
- Nuha Mahmoud
- Yoshikazu Sugimoto
- Thomas Efferth
- Heba Abdel-Aziz
- DOI
- 10.3389/fphar.2018.00481
- eISSN
- 1663-9812
- Zeitschrift
- Frontiers in Pharmacology
- Online publication date
- 2018
- Status
- Published online
- Herausgeber
- Frontiers Media SA
- Herausgeber URL
- http://dx.doi.org/10.3389/fphar.2018.00481
- Datum der Datenerfassung
- 2018
- Titel
- Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR)
- Ausgabe der Zeitschrift
- 9
Data source: Crossref
- Abstract
- Betulinic acid (BetA) is a naturally occurring pentacyclic triterpene isolated from the outer bark of white-barked birch trees and many other medicinal plants. Here, we studied betulinic acid's cytotoxic activity against drug-resistant tumor cell lines. P-glycoprotein (<i>MDR1/ABCB1</i>) and BCRP (<i>ABCG2</i>) are known ATP-binding cassette (ABC) drug transporters that mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. Constitutive activation of the EGF receptor is tightly linked to the development of chemotherapeutic resistance. BetA inhibited P-gp, BCRP, ABCB5 and mutation activated EGFR overexpressing cells with similar efficacy as their drug-sensitive parental counterparts. Furthermore, the mRNA expressions of ABCB1, BCRP, ABCB5 and EGFR were not related to the 50% inhibition concentrations (IC<sub>50</sub>) for BetA in a panel of 60 cell lines of the National Cancer Institute (NCI), USA. In addition to well-established MDR mechanisms, we attempted to identify other molecular mechanisms that play a role in mediating BetA's cytotoxic activity. For this reason, we performed COMPARE and hierarchical cluster analyses of the transcriptome-wide microarray-based mRNA expression of the NCI cell lines panel. Various genes significantly correlating to BetA's activity were involved in different biological processes, e.g., cell cycle regulation, microtubule formation, signal transduction, transcriptional regulation, chromatin remodeling, cell adhesion, tumor suppression, ubiquitination and proteasome degradation. Immunoblotting and <i>in silico</i> analyses revealed that the inhibition of AMFR activity might be one of the mechanisms for BetA to overcome MDR phenotypes. In conclusion, BetA may have therapeutic potential for the treatment of refractory tumors.
- Addresses
- Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, Germany.
- Autoren
- Mohamed EM Saeed
- Nuha Mahmoud
- Yoshikazu Sugimoto
- Thomas Efferth
- Heba Abdel-Aziz
- DOI
- 10.3389/fphar.2018.00481
- eISSN
- 1663-9812
- Externe Identifier
- PubMed Identifier: 29867487
- PubMed Central ID: PMC5962668
- Open access
- true
- ISSN
- 1663-9812
- Zeitschrift
- Frontiers in pharmacology
- Sprache
- eng
- Medium
- Electronic-eCollection
- Online publication date
- 2018
- Open access status
- Open Access
- Paginierung
- 481
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2018
- Titel
- Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR).
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 9
Files
https://www.frontiersin.org/articles/10.3389/fphar.2018.00481/pdf https://europepmc.org/articles/PMC5962668?pdf=render
Data source: Europe PubMed Central
- Abstract
- Betulinic acid (BetA) is a naturally occurring pentacyclic triterpene isolated from the outer bark of white-barked birch trees and many other medicinal plants. Here, we studied betulinic acid's cytotoxic activity against drug-resistant tumor cell lines. P-glycoprotein (MDR1/ABCB1) and BCRP (ABCG2) are known ATP-binding cassette (ABC) drug transporters that mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. Constitutive activation of the EGF receptor is tightly linked to the development of chemotherapeutic resistance. BetA inhibited P-gp, BCRP, ABCB5 and mutation activated EGFR overexpressing cells with similar efficacy as their drug-sensitive parental counterparts. Furthermore, the mRNA expressions of ABCB1, BCRP, ABCB5 and EGFR were not related to the 50% inhibition concentrations (IC50) for BetA in a panel of 60 cell lines of the National Cancer Institute (NCI), USA. In addition to well-established MDR mechanisms, we attempted to identify other molecular mechanisms that play a role in mediating BetA's cytotoxic activity. For this reason, we performed COMPARE and hierarchical cluster analyses of the transcriptome-wide microarray-based mRNA expression of the NCI cell lines panel. Various genes significantly correlating to BetA's activity were involved in different biological processes, e.g., cell cycle regulation, microtubule formation, signal transduction, transcriptional regulation, chromatin remodeling, cell adhesion, tumor suppression, ubiquitination and proteasome degradation. Immunoblotting and in silico analyses revealed that the inhibition of AMFR activity might be one of the mechanisms for BetA to overcome MDR phenotypes. In conclusion, BetA may have therapeutic potential for the treatment of refractory tumors.
- Date of acceptance
- 2018
- Autoren
- Mohamed EM Saeed
- Nuha Mahmoud
- Yoshikazu Sugimoto
- Thomas Efferth
- Heba Abdel-Aziz
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/29867487
- DOI
- 10.3389/fphar.2018.00481
- Externe Identifier
- PubMed Central ID: PMC5962668
- ISSN
- 1663-9812
- Zeitschrift
- Front Pharmacol
- Schlüsselwörter
- autocrine motility factor receptor (AMFR)
- bioinformatics
- cancer
- drug resistance
- microarray
- pharmacogenomics
- phytotherapy
- triterpene
- Sprache
- eng
- Country
- Switzerland
- Paginierung
- 481
- Datum der Veröffentlichung
- 2018
- Status
- Published online
- Titel
- Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR).
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 9
Data source: PubMed
- Beziehungen:
- Property of