Epimagnolin A, a tetrahydrofurofuranoid lignan from Magnolia fargesii, reverses ABCB1-mediated drug resistance

Publication type:
Journal article
Metadata:
Autoren
  • Yuji Mitani
  • Kazuhiro Satake
  • Megumi Tsukamoto
  • Ichiro Nakamura
  • Onat Kadioglu
  • Toshiaki Teruya
  • Takayuki Yonezawa
  • Cha Byung-Yoon
  • Thomas Efferth
  • Woo Je-Tae
  • Hiroshi Nakagawa
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000451438300013&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phymed.2018.06.030
Externe Identifier
  • Clarivate Analytics Document Solution ID: HB9UH
  • PubMed Identifier: 30466608
ISSN
0944-7113
Zeitschrift
PHYTOMEDICINE
Schlüsselwörter
  • ATP-binding cassette (ABC) transporter
  • ABCB1
  • P-glycoprotein
  • Epimagnolin A
  • Magnolia fargesii
  • Magnoliae Flos
Paginierung
112 - 119
Datum der Veröffentlichung
2018
Status
Published
Titel
Epimagnolin A, a tetrahydrofurofuranoid lignan from <i>Magnolia fargesii</i>, reverses ABCB1-mediated drug resistance
Sub types
  • Article
Ausgabe der Zeitschrift
51

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Yuji Mitani
  • Kazuhiro Satake
  • Megumi Tsukamoto
  • Ichiro Nakamura
  • Onat Kadioglu
  • Toshiaki Teruya
  • Takayuki Yonezawa
  • Byung-Yoon Cha
  • Thomas Efferth
  • Je-Tae Woo
  • Hiroshi Nakagawa
DOI
10.1016/j.phymed.2018.06.030
ISSN
0944-7113
Zeitschrift
Phytomedicine
Sprache
en
Paginierung
112 - 119
Datum der Veröffentlichung
2018
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phymed.2018.06.030
Datum der Datenerfassung
2022
Titel
Epimagnolin A, a tetrahydrofurofuranoid lignan from Magnolia fargesii, reverses ABCB1-mediated drug resistance
Ausgabe der Zeitschrift
51

Data source: Crossref

Abstract
<h4>Background</h4>Epimagnolin A is an ingredient of the Chinese crude drug Shin-i, derived from the dried flower buds of Magnolia fargesii and Magnolia flos, which has been traditionally used for the treatment of allergic rhinitis and nasal congestion, empyema, and sinusitis. The pharmacokinetic activity of epimagnolin A remains to be evaluated.<h4>Purpose</h4>In this study, we examined the possible interactions of epimagnolin A with human ATP-binding cassette (ABC) transporter ABCB1, a membrane protein vital in regulating the pharmacokinetics of drugs and xenobiotics.<h4>Study design/methods</h4>The interaction of epimagnolin A with ABCB1 was evaluated in calcein, ATPase, and MTT assays by using Flp-In-293/ABCB1 cells and purified ABCB1 and simulated in molecular docking studies.<h4>Results</h4>Epimagnolin A inhibited calcein export by Flp-In-293/ABCB1 cells in a concentration-dependent manner in a calcein assay. ATPase assay revealed a concentration-dependent stimulation of the ATPase activity of ABCB1 by epimagnolin A. Epimagnolin A also showed saturation kinetics in the relationship between the compound-stimulated ATPase activity and the compound concentration, suggesting Michaelis-Menten kinetics similar to those of the control drug, verapamil. K<sub>m</sub> and V<sub>max</sub> values were calculated from Hanes-Woolf plots of (compound concentration) × (compound-stimulated ATPase activity)<sup>-1</sup> vs. (compound concentration); the K<sub>m</sub> of epimagnolin and verapamil was 42.9 ± 7.53  μM and 12.3 ± 4.79  μM, respectively, and the corresponding V<sub>max</sub> values were 156 ± 15.0  μM and 109 ± 3.18  μM. Molecular docking studies on human ABCB1 showed that epimagnolin A docked to the same binding pocket as verapamil, and 3-(4,5-dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays showed that the sensitivities of Flp-In-293/ABCB1 cells against anti-cancer drugs were enhanced upon exposure to 10  μM epimagnolin A.<h4>Conclusion</h4>These results strongly suggest that epimagnolin A affects the transport activity of ABCB1 as a substrate.
Addresses
  • Department of Applied Biological Chemistry, Graduate School of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan.
Autoren
  • Yuji Mitani
  • Kazuhiro Satake
  • Megumi Tsukamoto
  • Ichiro Nakamura
  • Onat Kadioglu
  • Toshiaki Teruya
  • Takayuki Yonezawa
  • Byung-Yoon Cha
  • Thomas Efferth
  • Je-Tae Woo
  • Hiroshi Nakagawa
DOI
10.1016/j.phymed.2018.06.030
eISSN
1618-095X
Externe Identifier
  • PubMed Identifier: 30466608
Funding acknowledgements
  • Chubu University Grant D: DII28IIM02
  • Grant-in-Aid for Scientific Research (B) and (C) (JSPS KAKENHI: 16K00879
  • Grant-in-Aid for Scientific Research (B) and (C) (JSPS KAKENHI: 26293024
Open access
false
ISSN
0944-7113
Zeitschrift
Phytomedicine : international journal of phytotherapy and phytopharmacology
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Magnolia
  • Verapamil
  • Lignans
  • Antineoplastic Agents, Phytogenic
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Adenosine Triphosphatases
  • Molecular Docking Simulation
  • ATP Binding Cassette Transporter, Subfamily B
Sprache
eng
Medium
Print-Electronic
Online publication date
2018
Paginierung
112 - 119
Datum der Veröffentlichung
2018
Status
Published
Datum der Datenerfassung
2018
Titel
Epimagnolin A, a tetrahydrofurofuranoid lignan from Magnolia fargesii, reverses ABCB1-mediated drug resistance.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
51

Data source: Europe PubMed Central

Abstract
BACKGROUND: Epimagnolin A is an ingredient of the Chinese crude drug Shin-i, derived from the dried flower buds of Magnolia fargesii and Magnolia flos, which has been traditionally used for the treatment of allergic rhinitis and nasal congestion, empyema, and sinusitis. The pharmacokinetic activity of epimagnolin A remains to be evaluated. PURPOSE: In this study, we examined the possible interactions of epimagnolin A with human ATP-binding cassette (ABC) transporter ABCB1, a membrane protein vital in regulating the pharmacokinetics of drugs and xenobiotics. STUDY DESIGN/METHODS: The interaction of epimagnolin A with ABCB1 was evaluated in calcein, ATPase, and MTT assays by using Flp-In-293/ABCB1 cells and purified ABCB1 and simulated in molecular docking studies. RESULTS: Epimagnolin A inhibited calcein export by Flp-In-293/ABCB1 cells in a concentration-dependent manner in a calcein assay. ATPase assay revealed a concentration-dependent stimulation of the ATPase activity of ABCB1 by epimagnolin A. Epimagnolin A also showed saturation kinetics in the relationship between the compound-stimulated ATPase activity and the compound concentration, suggesting Michaelis-Menten kinetics similar to those of the control drug, verapamil. Km and Vmax values were calculated from Hanes-Woolf plots of (compound concentration) × (compound-stimulated ATPase activity)-1 vs. (compound concentration); the Km of epimagnolin and verapamil was 42.9 ± 7.53  μM and 12.3 ± 4.79  μM, respectively, and the corresponding Vmax values were 156 ± 15.0  μM and 109 ± 3.18  μM. Molecular docking studies on human ABCB1 showed that epimagnolin A docked to the same binding pocket as verapamil, and 3-(4,5-dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays showed that the sensitivities of Flp-In-293/ABCB1 cells against anti-cancer drugs were enhanced upon exposure to 10  μM epimagnolin A. CONCLUSION: These results strongly suggest that epimagnolin A affects the transport activity of ABCB1 as a substrate.
Date of acceptance
2018
Autoren
  • Yuji Mitani
  • Kazuhiro Satake
  • Megumi Tsukamoto
  • Ichiro Nakamura
  • Onat Kadioglu
  • Toshiaki Teruya
  • Takayuki Yonezawa
  • Byung-Yoon Cha
  • Thomas Efferth
  • Je-Tae Woo
  • Hiroshi Nakagawa
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/30466608
DOI
10.1016/j.phymed.2018.06.030
eISSN
1618-095X
Zeitschrift
Phytomedicine
Schlüsselwörter
  • ABC
  • ABCB1
  • ATP-binding cassette
  • ATP-binding cassette (ABC) transporter
  • Epimagnolin A
  • MDR
  • Magnolia fargesii
  • Magnoliae Flos
  • P-glycoprotein
  • P-gp
  • multidrug resistance
  • ATP Binding Cassette Transporter, Subfamily B
  • Adenosine Triphosphatases
  • Antineoplastic Agents, Phytogenic
  • Cell Line, Tumor
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Humans
  • Lignans
  • Magnolia
  • Molecular Docking Simulation
  • Verapamil
Sprache
eng
Country
Germany
Paginierung
112 - 119
PII
S0944-7113(18)30218-6
Datum der Veröffentlichung
2018
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2019
Titel
Epimagnolin A, a tetrahydrofurofuranoid lignan from Magnolia fargesii, reverses ABCB1-mediated drug resistance.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
51

Data source: PubMed

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