Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells

Publication type:
Journal article
Metadata:
Autoren
  • Edna Ooko
  • Mohamed EM Saeed
  • Onat Kadioglu
  • Shabnam Sarvi
  • Merve Colak
  • Kaoutar Elmasaoudi
  • Rabab Janah
  • Henry J Greten
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000362801400010&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phymed.2015.08.002
Externe Identifier
  • Clarivate Analytics Document Solution ID: CT4TY
  • PubMed Identifier: 26407947
ISSN
0944-7113
Ausgabe der Veröffentlichung
11
Zeitschrift
PHYTOMEDICINE
Schlüsselwörter
  • Cancer
  • Cell death
  • Iron
  • Microarray
  • Pharmacogenomics
Paginierung
1045 - 1054
Datum der Veröffentlichung
2015
Status
Published
Titel
Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells
Sub types
  • Article
Ausgabe der Zeitschrift
22

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Edna Ooko
  • Mohamed EM Saeed
  • Onat Kadioglu
  • Shabnam Sarvi
  • Merve Colak
  • Kaoutar Elmasaoudi
  • Rabab Janah
  • Henry J Greten
  • Thomas Efferth
DOI
10.1016/j.phymed.2015.08.002
ISSN
0944-7113
Ausgabe der Veröffentlichung
11
Zeitschrift
Phytomedicine
Sprache
en
Paginierung
1045 - 1054
Datum der Veröffentlichung
2015
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phymed.2015.08.002
Datum der Datenerfassung
2018
Titel
Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells
Ausgabe der Zeitschrift
22

Data source: Crossref

Abstract
<h4>Background</h4>Apoptosis and other forms of cell death have been intensively investigated in the past years to explain the mode of action of synthetic anticancer drugs and natural products. Recently, a new form of cell death emerged, which was termed ferroptosis, because it depends on intracellular iron. Here, the role of genes involved in iron metabolism and homeostasis for the cytotoxicity of ten artemisinin derivatives have been systematically investigated.<h4>Material and methods</h4>Log10IC50 values of 10 artemisinin derivatives (artesunate, artemether, arteether, artenimol, artemisitene, arteanuin B, another monomeric artemisinin derivative and three artemisinin dimer molecules) were correlated to the microarray-based mRNA expression of 30 iron-related genes in 60 cell lines of the National Cancer Institute (NCI, USA) as determined in 218 different microarray hybridization experiments. The effect of desferoxamine and ferrostatin-1 on the cytotoxicity of artenimol of CCRF-CEM cells was determined by resazurin assays. The mRNA expression of TFRC was exemplarily validated by immunohistochemical detection of transferrin receptor protein expression.<h4>Results</h4>The mRNA expression of 20 genes represented by 59 different cDNA clones significantly correlated to the log10IC50 values for the artemisinins, including genes encoding transferrin (TF), transferrin receptors 1 and 2 (TFRC, TFR2), cerulopasmin (CP), lactoferrin (LTF) and others. The ferroptosis inhibitor ferrostatin-1 and the iron chelator deferoxamine led to a significantly reduced cytotoxicity of artenimol, indicating ferroptosis as cell death mode.<h4>Conclusion</h4>The numerous iron-related genes, whose expression correlated with the response to artemisinin derivatives speak in factor for the relevance of iron for the cytotoxic activity of these compounds. Treatment with ferroptosis-inducing agents such as artemisinin derivatives represents an attractive strategy for cancer therapy. Pre-therapeutic determination of iron-related genes may indicate tumor sensitivity to artemisinins. Ferroptosis induced by artemisinin-type drugs deserve further investigation for individualized tumor therapy.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Autoren
  • Edna Ooko
  • Mohamed EM Saeed
  • Onat Kadioglu
  • Shabnam Sarvi
  • Merve Colak
  • Kaoutar Elmasaoudi
  • Rabab Janah
  • Henry J Greten
  • Thomas Efferth
  • Thomas Efferth
DOI
10.1016/j.phymed.2015.08.002
eISSN
1618-095X
Externe Identifier
  • PubMed Identifier: 26407947
Open access
false
ISSN
0944-7113
Ausgabe der Veröffentlichung
11
Zeitschrift
Phytomedicine : international journal of phytotherapy and phytopharmacology
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Iron
  • Phenylenediamines
  • Cyclohexylamines
  • Deferoxamine
  • Artemisinins
  • Oligonucleotide Array Sequence Analysis
  • Inhibitory Concentration 50
  • Cell Death
  • Apoptosis
  • Gene Expression Regulation, Neoplastic
  • Molecular Structure
  • Artesunate
  • Artemether
Sprache
eng
Medium
Print-Electronic
Online publication date
2015
Paginierung
1045 - 1054
Datum der Veröffentlichung
2015
Status
Published
Datum der Datenerfassung
2015
Titel
Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
22

Data source: Europe PubMed Central

Abstract
BACKGROUND: Apoptosis and other forms of cell death have been intensively investigated in the past years to explain the mode of action of synthetic anticancer drugs and natural products. Recently, a new form of cell death emerged, which was termed ferroptosis, because it depends on intracellular iron. Here, the role of genes involved in iron metabolism and homeostasis for the cytotoxicity of ten artemisinin derivatives have been systematically investigated. MATERIAL AND METHODS: Log10IC50 values of 10 artemisinin derivatives (artesunate, artemether, arteether, artenimol, artemisitene, arteanuin B, another monomeric artemisinin derivative and three artemisinin dimer molecules) were correlated to the microarray-based mRNA expression of 30 iron-related genes in 60 cell lines of the National Cancer Institute (NCI, USA) as determined in 218 different microarray hybridization experiments. The effect of desferoxamine and ferrostatin-1 on the cytotoxicity of artenimol of CCRF-CEM cells was determined by resazurin assays. The mRNA expression of TFRC was exemplarily validated by immunohistochemical detection of transferrin receptor protein expression. RESULTS: The mRNA expression of 20 genes represented by 59 different cDNA clones significantly correlated to the log10IC50 values for the artemisinins, including genes encoding transferrin (TF), transferrin receptors 1 and 2 (TFRC, TFR2), cerulopasmin (CP), lactoferrin (LTF) and others. The ferroptosis inhibitor ferrostatin-1 and the iron chelator deferoxamine led to a significantly reduced cytotoxicity of artenimol, indicating ferroptosis as cell death mode. CONCLUSION: The numerous iron-related genes, whose expression correlated with the response to artemisinin derivatives speak in factor for the relevance of iron for the cytotoxic activity of these compounds. Treatment with ferroptosis-inducing agents such as artemisinin derivatives represents an attractive strategy for cancer therapy. Pre-therapeutic determination of iron-related genes may indicate tumor sensitivity to artemisinins. Ferroptosis induced by artemisinin-type drugs deserve further investigation for individualized tumor therapy.
Date of acceptance
2015
Autoren
  • Edna Ooko
  • Mohamed EM Saeed
  • Onat Kadioglu
  • Shabnam Sarvi
  • Merve Colak
  • Kaoutar Elmasaoudi
  • Rabab Janah
  • Henry J Greten
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/26407947
DOI
10.1016/j.phymed.2015.08.002
eISSN
1618-095X
Ausgabe der Veröffentlichung
11
Zeitschrift
Phytomedicine
Schlüsselwörter
  • Cancer
  • Cell death
  • Iron
  • Microarray
  • Pharmacogenomics
  • Apoptosis
  • Artemether
  • Artemisinins
  • Artesunate
  • Cell Death
  • Cell Line, Tumor
  • Cyclohexylamines
  • Deferoxamine
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitory Concentration 50
  • Iron
  • Molecular Structure
  • Oligonucleotide Array Sequence Analysis
  • Phenylenediamines
Sprache
eng
Country
Germany
Paginierung
1045 - 1054
PII
S0944-7113(15)00237-8
Datum der Veröffentlichung
2015
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2015
Titel
Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
22

Data source: PubMed

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