Role of Transferrin Receptor and the ABC Transporters ABCB6 and ABCB7 for Resistance and Differentiation of Tumor Cells towards Artesunate

Publication type:
Journal article
Metadata:
Autoren
  • Gerhard Kelter
  • Daniel Steinbach
  • Venkata Badireenath Konkimalla
  • Tsuyoshi Tahara
  • Shigeru Taketani
  • Heinz-Herbert Fiebig
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000207455400015&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1371/journal.pone.0000798
Externe Identifier
  • Clarivate Analytics Document Solution ID: V10HP
  • PubMed Identifier: 17726528
ISSN
1932-6203
Ausgabe der Veröffentlichung
8
Zeitschrift
PLOS ONE
Artikelnummer
ARTN e798
Datum der Veröffentlichung
2007
Status
Published
Titel
Role of Transferrin Receptor and the ABC Transporters ABCB6 and ABCB7 for Resistance and Differentiation of Tumor Cells towards Artesunate
Sub types
  • Article
Ausgabe der Zeitschrift
2

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Gerhard Kelter
  • Daniel Steinbach
  • Venkata Badireenath Konkimalla
  • Tsuyoshi Tahara
  • Shigeru Taketani
  • Heinz-Herbert Fiebig
  • Thomas Efferth
DOI
10.1371/journal.pone.0000798
Editoren
  • Mikhail Blagosklonny
eISSN
1932-6203
Ausgabe der Veröffentlichung
8
Zeitschrift
PLoS ONE
Sprache
en
Online publication date
2007
Paginierung
e798 - e798
Status
Published online
Herausgeber
Public Library of Science (PLoS)
Herausgeber URL
http://dx.doi.org/10.1371/journal.pone.0000798
Datum der Datenerfassung
2019
Titel
Role of Transferrin Receptor and the ABC Transporters ABCB6 and ABCB7 for Resistance and Differentiation of Tumor Cells towards Artesunate
Ausgabe der Zeitschrift
2

Data source: Crossref

Abstract
The anti-malarial artesunate also exerts profound anti-cancer activity. The susceptibility of tumor cells to artesunate can be enhanced by ferrous iron. The transferrin receptor (TfR) is involved in iron uptake by internalization of transferrin and is over-expressed in rapidly growing tumors. The ATP-binding cassette (ABC) transporters ABCB6 and ABCB7 are also involved in iron homeostasis. To investigate whether these proteins play a role for sensitivity towards artesunate, Oncotest's 36 cell line panel was treated with artesunate or artesunate plus iron(II) glycine sulfate (Ferrosanol). The majority of cell lines showed increased inhibition rates, for the combination of artesunate plus iron(II) glycine sulfate compared to artesunate alone. However, in 11 out of the 36 cell lines the combination treatment was not superior. Cell lines with high TfR expression significantly correlated with high degrees of modulation indicating that high TfR expressing tumor cells would be more efficiently inhibited by this combination treatment than low TfR expressing ones. Furthermore, we found a significant relationship between cellular response to artesunate and TfR expression in 55 cell lines of the National Cancer Institute (NCI), USA. A significant correlation was also found for ABCB6, but not for ABCB7 in the NCI panel. Artesunate treatment of human CCRF-CEM leukemia and MCF7 breast cancer cells induced ABCB6 expression but repressed ABCB7 expression. Finally, artesunate inhibited proliferation and differentiation of mouse erythroleukemia (MEL) cells. Down-regulation of ABCB6 by antisense oligonucleotides inhibited differentiation of MEL cells indicating that artesunate and ABCB6 may cooperate. In conclusion, our results indicate that ferrous iron improves the activity of artesunate in some but not all tumor cell lines. Several factors involved in iron homeostasis such as TfR and ABCB6 may contribute to this effect.
Addresses
  • Oncotest GmbH, Institute of Experimental Oncology, Freiburg, Germany.
Autoren
  • Gerhard Kelter
  • Daniel Steinbach
  • Venkata Badireenath Konkimalla
  • Tsuyoshi Tahara
  • Shigeru Taketani
  • Heinz-Herbert Fiebig
  • Thomas Efferth
  • Thomas Efferth
DOI
10.1371/journal.pone.0000798
eISSN
1932-6203
Externe Identifier
  • PubMed Identifier: 17726528
  • PubMed Central ID: PMC1949049
Open access
true
ISSN
1932-6203
Ausgabe der Veröffentlichung
8
Zeitschrift
PloS one
Schlüsselwörter
  • Cell Line, Tumor
  • Animals
  • Humans
  • Mice
  • Artemisinins
  • ATP-Binding Cassette Transporters
  • Receptors, Transferrin
  • Antineoplastic Agents
  • Cell Differentiation
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • Artesunate
Sprache
eng
Medium
Electronic
Online publication date
2007
Open access status
Open Access
Paginierung
e798
Datum der Veröffentlichung
2007
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2007
Titel
Role of transferrin receptor and the ABC transporters ABCB6 and ABCB7 for resistance and differentiation of tumor cells towards artesunate.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
2

Files

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000798&type=printable https://europepmc.org/articles/PMC1949049?pdf=render

Data source: Europe PubMed Central

Abstract
The anti-malarial artesunate also exerts profound anti-cancer activity. The susceptibility of tumor cells to artesunate can be enhanced by ferrous iron. The transferrin receptor (TfR) is involved in iron uptake by internalization of transferrin and is over-expressed in rapidly growing tumors. The ATP-binding cassette (ABC) transporters ABCB6 and ABCB7 are also involved in iron homeostasis. To investigate whether these proteins play a role for sensitivity towards artesunate, Oncotest's 36 cell line panel was treated with artesunate or artesunate plus iron(II) glycine sulfate (Ferrosanol). The majority of cell lines showed increased inhibition rates, for the combination of artesunate plus iron(II) glycine sulfate compared to artesunate alone. However, in 11 out of the 36 cell lines the combination treatment was not superior. Cell lines with high TfR expression significantly correlated with high degrees of modulation indicating that high TfR expressing tumor cells would be more efficiently inhibited by this combination treatment than low TfR expressing ones. Furthermore, we found a significant relationship between cellular response to artesunate and TfR expression in 55 cell lines of the National Cancer Institute (NCI), USA. A significant correlation was also found for ABCB6, but not for ABCB7 in the NCI panel. Artesunate treatment of human CCRF-CEM leukemia and MCF7 breast cancer cells induced ABCB6 expression but repressed ABCB7 expression. Finally, artesunate inhibited proliferation and differentiation of mouse erythroleukemia (MEL) cells. Down-regulation of ABCB6 by antisense oligonucleotides inhibited differentiation of MEL cells indicating that artesunate and ABCB6 may cooperate. In conclusion, our results indicate that ferrous iron improves the activity of artesunate in some but not all tumor cell lines. Several factors involved in iron homeostasis such as TfR and ABCB6 may contribute to this effect.
Date of acceptance
2007
Autoren
  • Gerhard Kelter
  • Daniel Steinbach
  • Venkata Badireenath Konkimalla
  • Tsuyoshi Tahara
  • Shigeru Taketani
  • Heinz-Herbert Fiebig
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/17726528
DOI
10.1371/journal.pone.0000798
eISSN
1932-6203
Externe Identifier
  • PubMed Central ID: PMC1949049
Ausgabe der Veröffentlichung
8
Zeitschrift
PLoS One
Schlüsselwörter
  • ATP-Binding Cassette Transporters
  • Animals
  • Antineoplastic Agents
  • Artemisinins
  • Artesunate
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • Humans
  • Mice
  • Receptors, Transferrin
Sprache
eng
Country
United States
Paginierung
e798
Datum der Veröffentlichung
2007
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2010
Titel
Role of transferrin receptor and the ABC transporters ABCB6 and ABCB7 for resistance and differentiation of tumor cells towards artesunate.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
2

Data source: PubMed

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