Cytotoxicity and modes of action of 4′-hydroxy-2′,6′-dimethoxychalcone and other flavonoids toward drug-sensitive and multidrug-resistant cancer cell lines
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Victor Kuete
- Antoine HL Nkuete
- Armelle T Mbayeng
- Benjamin Wiench
- Hippolyte K Wabo
- Pierre Tane
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000344241200019&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.phymed.2014.08.001
- eISSN
- 1618-095X
- Externe Identifier
- Clarivate Analytics Document Solution ID: AS4JK
- PubMed Identifier: 25442273
- ISSN
- 0944-7113
- Ausgabe der Veröffentlichung
- 12
- Zeitschrift
- PHYTOMEDICINE
- Schlüsselwörter
- Apoptosis
- Chalcones
- Anticancer
- Flavanones
- Resistance
- Mode of action
- Paginierung
- 1651 - 1657
- Datum der Veröffentlichung
- 2014
- Status
- Published
- Titel
- Cytotoxicity and modes of action of 4′-hydroxy-2′,6′-dimethoxychalcone and other flavonoids toward drug-sensitive and multidrug-resistant cancer cell lines
- Sub types
- Article
- Ausgabe der Zeitschrift
- 21
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Victor Kuete
- Antoine HL Nkuete
- Armelle T Mbaveng
- Benjamin Wiench
- Hippolyte K Wabo
- Pierre Tane
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2014.08.001
- ISSN
- 0944-7113
- Ausgabe der Veröffentlichung
- 12
- Zeitschrift
- Phytomedicine
- Sprache
- en
- Paginierung
- 1651 - 1657
- Datum der Veröffentlichung
- 2014
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.phymed.2014.08.001
- Datum der Datenerfassung
- 2019
- Titel
- Cytotoxicity and modes of action of 4′-hydroxy-2′,6′-dimethoxychalcone and other flavonoids toward drug-sensitive and multidrug-resistant cancer cell lines
- Ausgabe der Zeitschrift
- 21
Data source: Crossref
- Abstract
- <h4>Introduction</h4>Resistance of cancer to chemotherapy is a main cause in treatment failure. Naturally occurring chalcones possess a wide range of biological activities including anti-cancer effects. In this work, we evaluated the antiproliferative activity of three chalcones [4'-hydroxy-2',6'-dimethoxychalcone (1), cardamomin (2), 2',4'-dihydroxy-3',6'-dimethoxychalcone (3)], and four flavanones [(S)-(-)-pinostrobin (4), (S)-(-)-onysilin (5) and alpinetin (6)] toward nine cancer cell lines amongst which were multidrug resistant (MDR) types.<h4>Methods</h4>The resazurin reduction assay was used to detect the antiproliferative activity of the studied samples whilst flow cytometry for the mechanistic studies of the most active molecule (1).<h4>Results</h4>IC50 values in a range of 2.54 μM against CEM/ADR5000 leukemia cells to 58.63 μM toward hepatocarcinoma HepG2 cells were obtained with 1. The lowest IC50 values of 8.59 μM for 2 and 10.67 μM for 3 were found against CCRF-CEM cells leukemia cells, whilst the corresponding values were above 80 μM for 4 and 6. P-glycoprotein-expressing and multidrug-resistant CEM/ADR5000 cells were much more sensitive toward compound 1 than toward doxorubicin and low cross-resistance or even collateral sensitivity was observed in other drug-resistent cell lines to this compound. Normal liver AML12 cells were more resistant to the studied compounds than HepG2 liver cancer cells, indicating tumor specificity at least to some extent. Compound 1 arrested the cell cycle between Go/G1 phase, strongly induced apoptosis via disrupted mitochondrial membrane potential (MMP) and increased production of reactive oxygen species (ROS) in the studied leukemia cell line.<h4>Conclusions</h4>Chalcone 1 was the best tested cytotoxic molecule and further studies will be performed in order to envisage its possible use in the fight against multifactorial resistant cancer cells.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany; Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
- Autoren
- Victor Kuete
- Antoine HL Nkuete
- Armelle T Mbaveng
- Benjamin Wiench
- Hippolyte K Wabo
- Pierre Tane
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2014.08.001
- eISSN
- 1618-095X
- Externe Identifier
- PubMed Identifier: 25442273
- Open access
- false
- ISSN
- 0944-7113
- Ausgabe der Veröffentlichung
- 12
- Zeitschrift
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Polygonum
- Reactive Oxygen Species
- Chalcones
- Flavonoids
- Plant Extracts
- Antineoplastic Agents, Phytogenic
- Inhibitory Concentration 50
- Drug Resistance, Multiple
- Apoptosis
- Molecular Structure
- Drug Resistance, Neoplasm
- Membrane Potential, Mitochondrial
- Hep G2 Cells
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2014
- Paginierung
- 1651 - 1657
- Datum der Veröffentlichung
- 2014
- Status
- Published
- Datum der Datenerfassung
- 2014
- Titel
- Cytotoxicity and modes of action of 4'-hydroxy-2',6'-dimethoxychalcone and other flavonoids toward drug-sensitive and multidrug-resistant cancer cell lines.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 21
Data source: Europe PubMed Central
- Abstract
- INTRODUCTION: Resistance of cancer to chemotherapy is a main cause in treatment failure. Naturally occurring chalcones possess a wide range of biological activities including anti-cancer effects. In this work, we evaluated the antiproliferative activity of three chalcones [4'-hydroxy-2',6'-dimethoxychalcone (1), cardamomin (2), 2',4'-dihydroxy-3',6'-dimethoxychalcone (3)], and four flavanones [(S)-(-)-pinostrobin (4), (S)-(-)-onysilin (5) and alpinetin (6)] toward nine cancer cell lines amongst which were multidrug resistant (MDR) types. METHODS: The resazurin reduction assay was used to detect the antiproliferative activity of the studied samples whilst flow cytometry for the mechanistic studies of the most active molecule (1). RESULTS: IC50 values in a range of 2.54 μM against CEM/ADR5000 leukemia cells to 58.63 μM toward hepatocarcinoma HepG2 cells were obtained with 1. The lowest IC50 values of 8.59 μM for 2 and 10.67 μM for 3 were found against CCRF-CEM cells leukemia cells, whilst the corresponding values were above 80 μM for 4 and 6. P-glycoprotein-expressing and multidrug-resistant CEM/ADR5000 cells were much more sensitive toward compound 1 than toward doxorubicin and low cross-resistance or even collateral sensitivity was observed in other drug-resistent cell lines to this compound. Normal liver AML12 cells were more resistant to the studied compounds than HepG2 liver cancer cells, indicating tumor specificity at least to some extent. Compound 1 arrested the cell cycle between Go/G1 phase, strongly induced apoptosis via disrupted mitochondrial membrane potential (MMP) and increased production of reactive oxygen species (ROS) in the studied leukemia cell line. CONCLUSIONS: Chalcone 1 was the best tested cytotoxic molecule and further studies will be performed in order to envisage its possible use in the fight against multifactorial resistant cancer cells.
- Date of acceptance
- 2014
- Autoren
- Victor Kuete
- Antoine HL Nkuete
- Armelle T Mbaveng
- Benjamin Wiench
- Hippolyte K Wabo
- Pierre Tane
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/25442273
- DOI
- 10.1016/j.phymed.2014.08.001
- eISSN
- 1618-095X
- Ausgabe der Veröffentlichung
- 12
- Zeitschrift
- Phytomedicine
- Schlüsselwörter
- Anticancer
- Apoptosis
- Chalcones
- Flavanones
- Mode of action
- Resistance
- Antineoplastic Agents, Phytogenic
- Apoptosis
- Cell Line, Tumor
- Chalcones
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- Flavonoids
- Hep G2 Cells
- Humans
- Inhibitory Concentration 50
- Membrane Potential, Mitochondrial
- Molecular Structure
- Plant Extracts
- Polygonum
- Reactive Oxygen Species
- Sprache
- eng
- Country
- Germany
- Paginierung
- 1651 - 1657
- PII
- S0944-7113(14)00316-X
- Datum der Veröffentlichung
- 2014
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2015
- Titel
- Cytotoxicity and modes of action of 4'-hydroxy-2',6'-dimethoxychalcone and other flavonoids toward drug-sensitive and multidrug-resistant cancer cell lines.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 21
Data source: PubMed
- Beziehungen:
- Property of