Selective inhibition of P-gp transporter by goniothalamin derivatives sensitizes resistant cancer cells to chemotherapy

Publication type:
Journal article
Metadata:
Autoren
  • Julia Sachs
  • Onat Kadioglu
  • Anja Weber
  • Vanessa Mundorf
  • Janina Betz
  • Thomas Efferth
  • Joerg Pietruszka
  • Nicole Teusch
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000455268900024&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1007/s11418-018-1230-x
eISSN
1861-0293
Externe Identifier
  • Clarivate Analytics Document Solution ID: HG8QQ
  • PubMed Identifier: 30066239
ISSN
1340-3443
Ausgabe der Veröffentlichung
1
Zeitschrift
JOURNAL OF NATURAL MEDICINES
Schlüsselwörter
  • Goniothalamin
  • Multidrug resistance
  • P-glycoprotein
  • Cancer chemotherapy
  • Resistance reversal
Paginierung
226 - 235
Datum der Veröffentlichung
2019
Status
Published
Titel
Selective inhibition of P-gp transporter by goniothalamin derivatives sensitizes resistant cancer cells to chemotherapy
Sub types
  • Article
Ausgabe der Zeitschrift
73

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Julia Sachs
  • Onat Kadioglu
  • Anja Weber
  • Vanessa Mundorf
  • Janina Betz
  • Thomas Efferth
  • Jörg Pietruszka
  • Nicole Teusch
DOI
10.1007/s11418-018-1230-x
eISSN
1861-0293
ISSN
1340-3443
Ausgabe der Veröffentlichung
1
Zeitschrift
Journal of Natural Medicines
Sprache
en
Online publication date
2018
Paginierung
226 - 235
Datum der Veröffentlichung
2019
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1007/s11418-018-1230-x
Datum der Datenerfassung
2020
Titel
Selective inhibition of P-gp transporter by goniothalamin derivatives sensitizes resistant cancer cells to chemotherapy
Ausgabe der Zeitschrift
73

Data source: Crossref

Abstract
Overexpression of efflux transporters of the ATP-binding cassette (ABC) transporter family, primarily P-glycoprotein (P-gp), is a frequent cause of multidrug resistance in cancer and leads to failure of current chemotherapies. Thus, identification of selective P-gp inhibitors might provide a basis for the development of novel anticancer drug candidates. The natural product goniothalamin and 21 derivatives were characterized regarding their ability to inhibit ABC transporter function. Among the goniothalamins, selective inhibitors of P-gp were discovered. The two most potent inhibitors (R)-3 and (S)-3 displayed the ability to increase intracellular accumulation of doxorubicin, thereby sensitizing P-gp-overexpressing tumor cells to chemotherapy by decreasing doxorubicin IC<sub>50</sub> value up to 15-fold. Molecular docking studies indicated these compounds to inhibit P-gp by acting as transporter substrates. In conclusion, our findings revealed a novel role of goniothalamin derivatives in reversing P-gp-mediated chemotherapy resistance.
Addresses
  • Bio-Pharmaceutical Chemistry and Molecular Pharmacology, Faculty of Applied Natural Sciences, Technische Hochschule Köln, CHEMPARK, Kaiser-Wilhelm-Allee,Geb. E39, 51368, Leverkusen, Germany.
Autoren
  • Julia Sachs
  • Onat Kadioglu
  • Anja Weber
  • Vanessa Mundorf
  • Janina Betz
  • Thomas Efferth
  • Jörg Pietruszka
  • Nicole Teusch
DOI
10.1007/s11418-018-1230-x
eISSN
1861-0293
Externe Identifier
  • PubMed Identifier: 30066239
Funding acknowledgements
  • German Federal Ministry for Economic Affairs and Energy: KF3279X01AJ3
Open access
false
ISSN
1340-3443
Ausgabe der Veröffentlichung
1
Zeitschrift
Journal of natural medicines
Schlüsselwörter
  • Humans
  • Neoplasms
  • Pyrones
  • Antineoplastic Agents
  • Drug Therapy
  • Drug Resistance, Neoplasm
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
Sprache
eng
Medium
Print-Electronic
Online publication date
2018
Paginierung
226 - 235
Datum der Veröffentlichung
2019
Status
Published
Datum der Datenerfassung
2018
Titel
Selective inhibition of P-gp transporter by goniothalamin derivatives sensitizes resistant cancer cells to chemotherapy.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
73

Data source: Europe PubMed Central

Abstract
Overexpression of efflux transporters of the ATP-binding cassette (ABC) transporter family, primarily P-glycoprotein (P-gp), is a frequent cause of multidrug resistance in cancer and leads to failure of current chemotherapies. Thus, identification of selective P-gp inhibitors might provide a basis for the development of novel anticancer drug candidates. The natural product goniothalamin and 21 derivatives were characterized regarding their ability to inhibit ABC transporter function. Among the goniothalamins, selective inhibitors of P-gp were discovered. The two most potent inhibitors (R)-3 and (S)-3 displayed the ability to increase intracellular accumulation of doxorubicin, thereby sensitizing P-gp-overexpressing tumor cells to chemotherapy by decreasing doxorubicin IC50 value up to 15-fold. Molecular docking studies indicated these compounds to inhibit P-gp by acting as transporter substrates. In conclusion, our findings revealed a novel role of goniothalamin derivatives in reversing P-gp-mediated chemotherapy resistance.
Date of acceptance
2018
Autoren
  • Julia Sachs
  • Onat Kadioglu
  • Anja Weber
  • Vanessa Mundorf
  • Janina Betz
  • Thomas Efferth
  • Jörg Pietruszka
  • Nicole Teusch
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/30066239
DOI
10.1007/s11418-018-1230-x
eISSN
1861-0293
Funding acknowledgements
  • German Federal Ministry for Economic Affairs and Energy: KF3279X01AJ3
Ausgabe der Veröffentlichung
1
Zeitschrift
J Nat Med
Schlüsselwörter
  • Cancer chemotherapy
  • Goniothalamin
  • Multidrug resistance
  • P-glycoprotein
  • Resistance reversal
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Drug Resistance, Neoplasm
  • Drug Therapy
  • Humans
  • Neoplasms
  • Pyrones
Sprache
eng
Country
Japan
Paginierung
226 - 235
PII
10.1007/s11418-018-1230-x
Datum der Veröffentlichung
2019
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2019
Titel
Selective inhibition of P-gp transporter by goniothalamin derivatives sensitizes resistant cancer cells to chemotherapy.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
73

Data source: PubMed

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