Cytotoxic flavonoids and isoflavonoids from Erythrina sigmoidea towards multi-factorial drug resistant cancer cells

Publication type:
Journal article
Metadata:
Autoren
  • Victor Kuete
  • Louis P Sandjo
  • Doriane E Djeussi
  • Maen Zeino
  • Guy MN Kwamou
  • Bonaventure Ngadjui
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000345142300001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1007/s10637-014-0137-y
eISSN
1573-0646
Externe Identifier
  • Clarivate Analytics Document Solution ID: AT7UI
  • PubMed Identifier: 25034000
ISSN
0167-6997
Ausgabe der Veröffentlichung
6
Zeitschrift
INVESTIGATIONAL NEW DRUGS
Schlüsselwörter
  • Flavonoids
  • Isoflavonoids
  • Leguminosae
  • Cytotoxicity
  • Cell cycle distribution
  • Mitochondrial membrane potential
  • Apoptosis
Paginierung
1053 - 1062
Datum der Veröffentlichung
2014
Status
Published
Titel
Cytotoxic flavonoids and isoflavonoids from <i>Erythrina sigmoidea</i> towards multi-factorial drug resistant cancer cells
Sub types
  • Article
Ausgabe der Zeitschrift
32

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Victor Kuete
  • Louis P Sandjo
  • Doriane E Djeussi
  • Maen Zeino
  • Guy MN Kwamou
  • Bonaventure Ngadjui
  • Thomas Efferth
DOI
10.1007/s10637-014-0137-y
eISSN
1573-0646
ISSN
0167-6997
Ausgabe der Veröffentlichung
6
Zeitschrift
Investigational New Drugs
Sprache
en
Online publication date
2014
Paginierung
1053 - 1062
Datum der Veröffentlichung
2014
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1007/s10637-014-0137-y
Datum der Datenerfassung
2023
Titel
Cytotoxic flavonoids and isoflavonoids from Erythrina sigmoidea towards multi-factorial drug resistant cancer cells
Ausgabe der Zeitschrift
32

Data source: Crossref

Abstract
<h4>Introduction</h4>Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds. This work was designed to assess the cytotoxicity and the mechanism of action of flavonoids abyssinone IV (1), atalantoflavone (3) and neocyclomorusin (6) and isoflavonoids sigmoidin I (2), sophorapterocarpan A (4), bidwillon A (5) and 6α-hydroxyphaseollidin (7) isolated from Erythrina sigmoidea against nine drug sensitive and multidrug resistant (MDR) cancer cell lines.<h4>Methods</h4>The resazurin reduction assay was used to evaluate the cytotoxicity of the studied compounds whilst caspase-Glo assay was used to detect the activation of caspases enzymes by 1, 2, 4 and 7. Cell cycle, mitochondrial membrane potential and levels of reactive oxygen species were all analyzed via flow cytometry.<h4>Results</h4>The pterocarpan isoflavonoid 7 displayed the best antiproliferative activity with the IC50 values below 10 μM obtained on the nine tested cancer cell lines. The IC50 values below 50 μM were also recorded with compounds 1, 2 and 4 against the nine cancer cell lines whilst 3, 5 and 6 showed selective activities. The IC50 values varied from 14.43 μM (against MDA-MB-231-pcDNA cells) to 20.65 μM [towards HCT116 (p53(+/+)) cells] for compound 1, from 4.24 μM (towards CCRF-CEM cells) to 30.98 μM (towards MDA-MB-231-BCRP cells) for 2, from 3.73 μM (towards CCRF-CEM cells) to 14.81 μM (against U87MG.ΔEGFR cells) for 4, from 3.36 μM (towards CCRF-CEM cells) to 6.44 μM (against HepG2 cells) for 7, and from 0.20 μM (against CCRF-CEM cells) and 195.12 μM (against CEM/ADR5000 cells) for the positive control drug, doxorubicin. Compared to their corresponding sensitive cell lines, collateral sensitivity was observed with HCT116 (p53(-/-)) to 1, 2, 4, 5, and 7 and with U87MG.ΔEGFR to 1 to 6. Compound 7 induced apoptosis in CCRF-CEM cells mediated by the activation of caspases 3/7, 8 and 9 and breakdown of MMP and increase in ROS production, whereas the apoptotic process induced by 1, 2 and 4 was mediated by the loss of MMP as well as increase in ROS production.<h4>Conclusions</h4>Compounds from Erythrina sigmoidea and mostly 6α-hydroxyphaseollidin are potential antiproliferative natural products that deserve more investigations to develop novel anticancer drugs against sensitive and otherwise drug-resistant phenotypes.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128, Mainz, Germany.
Autoren
  • Victor Kuete
  • Louis P Sandjo
  • Doriane E Djeussi
  • Maen Zeino
  • Guy MN Kwamou
  • Bonaventure Ngadjui
  • Thomas Efferth
  • Thomas Efferth
DOI
10.1007/s10637-014-0137-y
eISSN
1573-0646
Externe Identifier
  • PubMed Identifier: 25034000
Open access
false
ISSN
0167-6997
Ausgabe der Veröffentlichung
6
Zeitschrift
Investigational new drugs
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Erythrina
  • Plant Bark
  • Reactive Oxygen Species
  • Flavonoids
  • Caspases
  • Antineoplastic Agents
  • Drug Resistance, Multiple
  • Cell Cycle
  • Apoptosis
  • Drug Resistance, Neoplasm
  • Membrane Potential, Mitochondrial
Sprache
eng
Medium
Print-Electronic
Online publication date
2014
Paginierung
1053 - 1062
Datum der Veröffentlichung
2014
Status
Published
Datum der Datenerfassung
2014
Titel
Cytotoxic flavonoids and isoflavonoids from Erythrina sigmoidea towards multi-factorial drug resistant cancer cells.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
32

Data source: Europe PubMed Central

Abstract
INTRODUCTION: Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds. This work was designed to assess the cytotoxicity and the mechanism of action of flavonoids abyssinone IV (1), atalantoflavone (3) and neocyclomorusin (6) and isoflavonoids sigmoidin I (2), sophorapterocarpan A (4), bidwillon A (5) and 6α-hydroxyphaseollidin (7) isolated from Erythrina sigmoidea against nine drug sensitive and multidrug resistant (MDR) cancer cell lines. METHODS: The resazurin reduction assay was used to evaluate the cytotoxicity of the studied compounds whilst caspase-Glo assay was used to detect the activation of caspases enzymes by 1, 2, 4 and 7. Cell cycle, mitochondrial membrane potential and levels of reactive oxygen species were all analyzed via flow cytometry. RESULTS: The pterocarpan isoflavonoid 7 displayed the best antiproliferative activity with the IC50 values below 10 μM obtained on the nine tested cancer cell lines. The IC50 values below 50 μM were also recorded with compounds 1, 2 and 4 against the nine cancer cell lines whilst 3, 5 and 6 showed selective activities. The IC50 values varied from 14.43 μM (against MDA-MB-231-pcDNA cells) to 20.65 μM [towards HCT116 (p53(+/+)) cells] for compound 1, from 4.24 μM (towards CCRF-CEM cells) to 30.98 μM (towards MDA-MB-231-BCRP cells) for 2, from 3.73 μM (towards CCRF-CEM cells) to 14.81 μM (against U87MG.ΔEGFR cells) for 4, from 3.36 μM (towards CCRF-CEM cells) to 6.44 μM (against HepG2 cells) for 7, and from 0.20 μM (against CCRF-CEM cells) and 195.12 μM (against CEM/ADR5000 cells) for the positive control drug, doxorubicin. Compared to their corresponding sensitive cell lines, collateral sensitivity was observed with HCT116 (p53(-/-)) to 1, 2, 4, 5, and 7 and with U87MG.ΔEGFR to 1 to 6. Compound 7 induced apoptosis in CCRF-CEM cells mediated by the activation of caspases 3/7, 8 and 9 and breakdown of MMP and increase in ROS production, whereas the apoptotic process induced by 1, 2 and 4 was mediated by the loss of MMP as well as increase in ROS production. CONCLUSIONS: Compounds from Erythrina sigmoidea and mostly 6α-hydroxyphaseollidin are potential antiproliferative natural products that deserve more investigations to develop novel anticancer drugs against sensitive and otherwise drug-resistant phenotypes.
Date of acceptance
2014
Autoren
  • Victor Kuete
  • Louis P Sandjo
  • Doriane E Djeussi
  • Maen Zeino
  • Guy MN Kwamou
  • Bonaventure Ngadjui
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/25034000
DOI
10.1007/s10637-014-0137-y
eISSN
1573-0646
Ausgabe der Veröffentlichung
6
Zeitschrift
Invest New Drugs
Schlüsselwörter
  • Antineoplastic Agents
  • Apoptosis
  • Caspases
  • Cell Cycle
  • Cell Line, Tumor
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Erythrina
  • Flavonoids
  • Humans
  • Membrane Potential, Mitochondrial
  • Plant Bark
  • Reactive Oxygen Species
Sprache
eng
Country
United States
Paginierung
1053 - 1062
Datum der Veröffentlichung
2014
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2015
Titel
Cytotoxic flavonoids and isoflavonoids from Erythrina sigmoidea towards multi-factorial drug resistant cancer cells.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
32

Data source: PubMed

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