Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- T Efferth
- A Benakis
- MR Romero
- M Tomicic
- R Rauh
- D Steinbach
- R Häfer
- T Stamminger
- F Oesch
- B Kaina
- M Marschall
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000224011900011&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.freeradbiomed.2004.06.023
- eISSN
- 1873-4596
- Externe Identifier
- Clarivate Analytics Document Solution ID: 855YX
- PubMed Identifier: 15336316
- ISSN
- 0891-5849
- Ausgabe der Veröffentlichung
- 7
- Zeitschrift
- FREE RADICAL BIOLOGY AND MEDICINE
- Schlüsselwörter
- artemisinin
- artesunate
- transferrin
- iron(II)-glycine sulfate
- free radicals
- Paginierung
- 998 - 1009
- Datum der Veröffentlichung
- 2004
- Status
- Published
- Titel
- Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron
- Sub types
- Article
- Ausgabe der Zeitschrift
- 37
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Thomas Efferth
- Achille Benakis
- Marta R Romero
- Maja Tomicic
- Rolf Rauh
- Daniel Steinbach
- Ralf Häfer
- Thomas Stamminger
- Franz Oesch
- Bernd Kaina
- Manfred Marschall
- DOI
- 10.1016/j.freeradbiomed.2004.06.023
- ISSN
- 0891-5849
- Ausgabe der Veröffentlichung
- 7
- Zeitschrift
- Free Radical Biology and Medicine
- Sprache
- en
- Paginierung
- 998 - 1009
- Datum der Veröffentlichung
- 2004
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.freeradbiomed.2004.06.023
- Datum der Datenerfassung
- 2023
- Titel
- Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron
- Ausgabe der Zeitschrift
- 37
Data source: Crossref
- Abstract
- Iron(II) heme-mediated activation of the peroxide bond of artemisinins is thought to generate the radical oxygen species responsible for their antimalarial activity. We analyzed the role of ferrous iron in the cytotoxicity of artemisinins toward tumor cells. Iron(II)-glycine sulfate (Ferrosanol) and transferrin increased the cytotoxicity of free artesunate, artesunate microencapsulated in maltosyl-beta-cyclodextrin, and artemisinin toward CCRF-CEM leukemia and U373 astrocytoma cells 1.5- to 10.3-fold compared with that of artemisinins applied without iron. Growth inhibition by artesunate and ferrous iron correlated with induction of apoptosis. Cell cycle perturbations by artesunate and ferrous iron were not observed. Treatment of p53 wild-type TK6 and p53 mutated WTK1 lymphoblastic cells showed that mutational status of the tumor suppressor p53 did not influence sensitivity to artesunate. The effect of ferrous iron and transferrin was reversed by monoclonal antibody RVS10 against the transferrin receptor (TfR), which competes with transferrin for binding to TfR. CCRF-CEM and U373 cells expressed TfR in 95 and 48% of the cell population, respectively, whereas TfR expression in peripheral mononuclear blood cells of four healthy donors was confined to 0.4-1.3%. This indicates that artemisinins plus ferrous iron may affect tumor cells more than normal cells. The IC(50) values for a series of eight different artemisinin derivatives in 60 cell lines of the U.S. National Cancer Institute were correlated with the microarray mRNA expression of 12 genes involved in iron uptake and metabolism by Kendall's tau test to identify iron-responsive cellular factors enhancing the activity of artemisinins. This pointed to mitochondrial aconitase and ceruloplasmin (ferroxidase).
- Addresses
- Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany. thomas.efferth@zmbh.uni-heidelberg.de
- Autoren
- Thomas Efferth
- Thomas Efferth
- Achille Benakis
- Marta R Romero
- Maja Tomicic
- Rolf Rauh
- Daniel Steinbach
- Ralf Häfer
- Thomas Stamminger
- Franz Oesch
- Bernd Kaina
- Manfred Marschall
- DOI
- 10.1016/j.freeradbiomed.2004.06.023
- eISSN
- 1873-4596
- Externe Identifier
- PubMed Identifier: 15336316
- Open access
- false
- ISSN
- 0891-5849
- Ausgabe der Veröffentlichung
- 7
- Zeitschrift
- Free radical biology & medicine
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Neoplasms
- Iron
- Ferrous Compounds
- Artemisinins
- Receptors, Transferrin
- RNA, Messenger
- Antigens, CD
- Antigens, Differentiation, B-Lymphocyte
- Inhibitory Concentration 50
- Cell Proliferation
- Gene Expression Regulation
- Tumor Suppressor Protein p53
- Sprache
- eng
- Medium
- Paginierung
- 998 - 1009
- Datum der Veröffentlichung
- 2004
- Status
- Published
- Datum der Datenerfassung
- 2004
- Titel
- Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 37
Data source: Europe PubMed Central
- Abstract
- Iron(II) heme-mediated activation of the peroxide bond of artemisinins is thought to generate the radical oxygen species responsible for their antimalarial activity. We analyzed the role of ferrous iron in the cytotoxicity of artemisinins toward tumor cells. Iron(II)-glycine sulfate (Ferrosanol) and transferrin increased the cytotoxicity of free artesunate, artesunate microencapsulated in maltosyl-beta-cyclodextrin, and artemisinin toward CCRF-CEM leukemia and U373 astrocytoma cells 1.5- to 10.3-fold compared with that of artemisinins applied without iron. Growth inhibition by artesunate and ferrous iron correlated with induction of apoptosis. Cell cycle perturbations by artesunate and ferrous iron were not observed. Treatment of p53 wild-type TK6 and p53 mutated WTK1 lymphoblastic cells showed that mutational status of the tumor suppressor p53 did not influence sensitivity to artesunate. The effect of ferrous iron and transferrin was reversed by monoclonal antibody RVS10 against the transferrin receptor (TfR), which competes with transferrin for binding to TfR. CCRF-CEM and U373 cells expressed TfR in 95 and 48% of the cell population, respectively, whereas TfR expression in peripheral mononuclear blood cells of four healthy donors was confined to 0.4-1.3%. This indicates that artemisinins plus ferrous iron may affect tumor cells more than normal cells. The IC(50) values for a series of eight different artemisinin derivatives in 60 cell lines of the U.S. National Cancer Institute were correlated with the microarray mRNA expression of 12 genes involved in iron uptake and metabolism by Kendall's tau test to identify iron-responsive cellular factors enhancing the activity of artemisinins. This pointed to mitochondrial aconitase and ceruloplasmin (ferroxidase).
- Date of acceptance
- 2004
- Autoren
- Thomas Efferth
- Achille Benakis
- Marta R Romero
- Maja Tomicic
- Rolf Rauh
- Daniel Steinbach
- Ralf Häfer
- Thomas Stamminger
- Franz Oesch
- Bernd Kaina
- Manfred Marschall
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/15336316
- DOI
- 10.1016/j.freeradbiomed.2004.06.023
- ISSN
- 0891-5849
- Ausgabe der Veröffentlichung
- 7
- Zeitschrift
- Free Radic Biol Med
- Schlüsselwörter
- Antigens, CD
- Antigens, Differentiation, B-Lymphocyte
- Artemisinins
- Cell Line, Tumor
- Cell Proliferation
- Ferrous Compounds
- Gene Expression Regulation
- Humans
- Inhibitory Concentration 50
- Iron
- Neoplasms
- RNA, Messenger
- Receptors, Transferrin
- Tumor Suppressor Protein p53
- Sprache
- eng
- Country
- United States
- Paginierung
- 998 - 1009
- PII
- S0891-5849(04)00494-0
- Datum der Veröffentlichung
- 2004
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2005
- Titel
- Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 37
Data source: PubMed
- Autoren
- T EFFERTH
- Zeitschrift
- Free Radic Biol Med.
- Paginierung
- 998 - 1009
- Datum der Veröffentlichung
- 2004
- Titel
- Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron
- Ausgabe der Zeitschrift
- 37
Data source: CiNii EN
- Autoren
- T EFFERTH
- Zeitschrift
- Free Radic Biol Med.
- Paginierung
- 998 - 1009
- Datum der Veröffentlichung
- 2004
- Titel
- Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron
- Ausgabe der Zeitschrift
- 37
Data source: CiNii JP
- Beziehungen:
- Property of