Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera) against Multidrug-Resistant Tumor Cells

Publication type:
Journal article
Metadata:
Autoren
  • Onat Kadioglu
  • Betty YK Law
  • Simon WF Mok
  • Su-Wei Xu
  • Thomas Efferth
  • Vincent KW Wong
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000400639000001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3389/fphar.2017.00238
eISSN
1663-9812
Externe Identifier
  • Clarivate Analytics Document Solution ID: ET9PI
  • PubMed Identifier: 28529482
Zeitschrift
FRONTIERS IN PHARMACOLOGY
Schlüsselwörter
  • cancer
  • chemotherapy
  • drug resistance
  • natural products
  • neferine
  • P-glycoprotein
Artikelnummer
ARTN 238
Datum der Veröffentlichung
2017
Status
Published
Titel
Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (<i>Nelumbo nucifera</i>) against Multidrug-Resistant Tumor Cells
Sub types
  • Article
Ausgabe der Zeitschrift
8

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Onat Kadioglu
  • Betty YK Law
  • Simon WF Mok
  • Su-Wei Xu
  • Thomas Efferth
  • Vincent KW Wong
DOI
10.3389/fphar.2017.00238
eISSN
1663-9812
Zeitschrift
Frontiers in Pharmacology
Online publication date
2017
Status
Published online
Herausgeber
Frontiers Media SA
Herausgeber URL
http://dx.doi.org/10.3389/fphar.2017.00238
Datum der Datenerfassung
2017
Titel
Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera) against Multidrug-Resistant Tumor Cells
Ausgabe der Zeitschrift
8

Data source: Crossref

Abstract
Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (<i>Nelumbo nucifera</i> Gaertn), has been previously shown to have various anti-cancer effects. In the present study, we evaluated the effect of neferine in terms of P-glycoprotein (P-gp) inhibition via <i>in vitro</i> cytotoxicity assays, R123 uptake assays in drug-resistant cancer cells, <i>in silico</i> molecular docking analysis on human P-gp and <i>in silico</i> absorption, distribution, metabolism, and excretion (ADME), quantitative structure activity relationships (QSAR) and toxicity analyses. Lipinski rule of five were mainly considered for the ADME evaluation and the preset descriptors including number of hydrogen bond donor, acceptor, hERG IC<sub>50</sub>, logp, logD were considered for the QSAR analyses. Neferine revealed higher toxicity toward paclitaxel- and doxorubicin-resistant breast, lung or colon cancer cells, implying collateral sensitivity of these cells toward neferine. Increased R123 uptake was observed in a comparable manner to the control P-gp inhibitor, verapamil. Molecular docking analyses revealed that neferine still interacts with P-gp, even if R123 was pre-bound. Bioinformatical ADME and toxicity analyses revealed that neferine possesses the druggability parameters with no predicted toxicity. In conclusion, neferine may allocate the P-gp drug-binding pocket and prevent R123 binding in agreement with P-gp inhibition experiments, where neferine increased R123 uptake.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of MainzMainz, Germany.
Autoren
  • Onat Kadioglu
  • Betty YK Law
  • Simon WF Mok
  • Su-Wei Xu
  • Thomas Efferth
  • Thomas Efferth
  • Vincent KW Wong
DOI
10.3389/fphar.2017.00238
eISSN
1663-9812
Externe Identifier
  • PubMed Identifier: 28529482
  • PubMed Central ID: PMC5418350
Open access
true
ISSN
1663-9812
Zeitschrift
Frontiers in pharmacology
Sprache
eng
Medium
Electronic-eCollection
Online publication date
2017
Open access status
Open Access
Paginierung
238
Datum der Veröffentlichung
2017
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2017
Titel
Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (<i>Nelumbo nucifera</i>) against Multidrug-Resistant Tumor Cells.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
8

Files

https://www.frontiersin.org/articles/10.3389/fphar.2017.00238/pdf https://europepmc.org/articles/PMC5418350?pdf=render

Data source: Europe PubMed Central

Abstract
Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (Nelumbo nucifera Gaertn), has been previously shown to have various anti-cancer effects. In the present study, we evaluated the effect of neferine in terms of P-glycoprotein (P-gp) inhibition via in vitro cytotoxicity assays, R123 uptake assays in drug-resistant cancer cells, in silico molecular docking analysis on human P-gp and in silico absorption, distribution, metabolism, and excretion (ADME), quantitative structure activity relationships (QSAR) and toxicity analyses. Lipinski rule of five were mainly considered for the ADME evaluation and the preset descriptors including number of hydrogen bond donor, acceptor, hERG IC50, logp, logD were considered for the QSAR analyses. Neferine revealed higher toxicity toward paclitaxel- and doxorubicin-resistant breast, lung or colon cancer cells, implying collateral sensitivity of these cells toward neferine. Increased R123 uptake was observed in a comparable manner to the control P-gp inhibitor, verapamil. Molecular docking analyses revealed that neferine still interacts with P-gp, even if R123 was pre-bound. Bioinformatical ADME and toxicity analyses revealed that neferine possesses the druggability parameters with no predicted toxicity. In conclusion, neferine may allocate the P-gp drug-binding pocket and prevent R123 binding in agreement with P-gp inhibition experiments, where neferine increased R123 uptake.
Date of acceptance
2017
Autoren
  • Onat Kadioglu
  • Betty YK Law
  • Simon WF Mok
  • Su-Wei Xu
  • Thomas Efferth
  • Vincent KW Wong
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/28529482
DOI
10.3389/fphar.2017.00238
Externe Identifier
  • PubMed Central ID: PMC5418350
ISSN
1663-9812
Zeitschrift
Front Pharmacol
Schlüsselwörter
  • P-glycoprotein
  • cancer
  • chemotherapy
  • drug resistance
  • natural products
  • neferine
Sprache
eng
Country
Switzerland
Paginierung
238
Datum der Veröffentlichung
2017
Status
Published online
Titel
Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera) against Multidrug-Resistant Tumor Cells.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
8

Data source: PubMed

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