Molecular modes of action of artesunate in tumor cell lines

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • T Efferth
  • A Sauerbrey
  • A Olbrich
  • E Gebhart
  • P Rauch
  • HO Weber
  • JG Hengstler
  • ME Halatsch
  • M Volm
  • KD Tew
  • DD Ross
  • JO Funk
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000184220900022&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1124/mol.64.2.382
Externe Identifier
  • Clarivate Analytics Document Solution ID: 702JN
  • PubMed Identifier: 12869643
ISSN
0026-895X
Ausgabe der Veröffentlichung
2
Zeitschrift
MOLECULAR PHARMACOLOGY
Paginierung
382 - 394
Datum der Veröffentlichung
2003
Status
Published
Titel
Molecular modes of action of artesunate in tumor cell lines
Sub types
  • Article
Ausgabe der Zeitschrift
64

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Autoren
  • Thomas Efferth
  • Axel Sauerbrey
  • Armin Olbrich
  • Erich Gebhart
  • Pia Rauch
  • H Oliver Weber
  • Jan G Hengstler
  • Marc-Eric Halatsch
  • Manfred Volm
  • Kenneth D Tew
  • Douglas D Ross
  • Jens Oliver Funk
DOI
10.1124/mol.64.2.382
eISSN
1521-0111
ISSN
0026-895X
Ausgabe der Veröffentlichung
2
Zeitschrift
Molecular Pharmacology
Sprache
en
Online publication date
2003
Paginierung
382 - 394
Datum der Veröffentlichung
2003
Status
Published
Herausgeber
American Society for Pharmacology & Experimental Therapeutics (ASPET)
Herausgeber URL
http://dx.doi.org/10.1124/mol.64.2.382
Datum der Datenerfassung
2019
Titel
Molecular Modes of Action of Artesunate in Tumor Cell Lines
Ausgabe der Zeitschrift
64

Datenquelle: Crossref

Abstract
A profound cytotoxic action of the antimalarial, artesunate (ART), was identified against 55 cancer cell lines of the U.S. National Cancer Institute (NCI). The 50% inhibition concentrations (IC50 values) for ART correlated significantly to the cell doubling times (P = 0.00132) and the portion of cells in the G0/G1 (P = 0.02244) or S cell cycle phases (P = 0.03567). We selected mRNA expression data of 465 genes obtained by microarray hybridization from the NCI data base. These genes belong to different biological categories (drug resistance genes, DNA damage response and repair genes, oncogenes and tumor suppressor genes, apoptosis-regulating genes, proliferation-associated genes, and cytokines and cytokine-associated genes). The constitutive expression of 54 of 465 (=12%) genes correlated significantly to the IC50 values for ART. Hierarchical cluster analysis of these 12 genes allowed the differentiation of clusters with ART-sensitive or ART-resistant cell lines (P = 0.00017). For exemplary validation, cell lines transduced with 3 of the 12 genes were used to prove a causative relationship. The cDNAs for a deletion-mutated epidermal growth factor receptor (EGFR) and for gamma-glutamylcysteine synthetase increased resistance to ART. The conditional expression of the CDC25A gene using a tetracycline repressor expression vector increased sensitivity toward ART. Multidrug-resistant cells differentially expressing the MDR1, MRP1, or BCRP genes were not cross-resistant to ART. ART acts via p53-dependent and- independent pathways in isogenic p53+/+ p21WAF1/CIP1+/+, p53-/- p21WAF1/CIP1+/+, and p53+/+ p21WAF1/CIP1-/- colon carcinoma cells.
Addresses
  • Center for Molecular Biology of the University of Heidelberg (ZMBH), Heidelberg, Germany. thomas.efferth@web.de
Autoren
  • Thomas Efferth
  • Thomas Efferth
  • Axel Sauerbrey
  • Armin Olbrich
  • Erich Gebhart
  • Pia Rauch
  • H Oliver Weber
  • Jan G Hengstler
  • Marc-Eric Halatsch
  • Manfred Volm
  • Kenneth D Tew
  • Douglas D Ross
  • Jens Oliver Funk
DOI
10.1124/mol.64.2.382
eISSN
1521-0111
Externe Identifier
  • PubMed Identifier: 12869643
Funding acknowledgements
  • NCI NIH HHS: R01-CA77545
Open access
false
ISSN
0026-895X
Ausgabe der Veröffentlichung
2
Zeitschrift
Molecular pharmacology
Schlüsselwörter
  • Cell Line, Transformed
  • HL-60 Cells
  • Tumor Cells, Cultured
  • Animals
  • Humans
  • Sesquiterpenes
  • Artemisinins
  • RNA, Messenger
  • Antineoplastic Agents
  • Drug Screening Assays, Antitumor
  • Gene Expression Profiling
  • Drug Resistance, Multiple
  • Cell Cycle
  • Cell Division
  • Apoptosis
  • Tumor Suppressor Protein p53
  • Artesunate
Sprache
eng
Medium
Print
Paginierung
382 - 394
Datum der Veröffentlichung
2003
Status
Published
Datum der Datenerfassung
2003
Titel
Molecular modes of action of artesunate in tumor cell lines.
Sub types
  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Journal Article
Ausgabe der Zeitschrift
64

Datenquelle: Europe PubMed Central

Abstract
A profound cytotoxic action of the antimalarial, artesunate (ART), was identified against 55 cancer cell lines of the U.S. National Cancer Institute (NCI). The 50% inhibition concentrations (IC50 values) for ART correlated significantly to the cell doubling times (P = 0.00132) and the portion of cells in the G0/G1 (P = 0.02244) or S cell cycle phases (P = 0.03567). We selected mRNA expression data of 465 genes obtained by microarray hybridization from the NCI data base. These genes belong to different biological categories (drug resistance genes, DNA damage response and repair genes, oncogenes and tumor suppressor genes, apoptosis-regulating genes, proliferation-associated genes, and cytokines and cytokine-associated genes). The constitutive expression of 54 of 465 (=12%) genes correlated significantly to the IC50 values for ART. Hierarchical cluster analysis of these 12 genes allowed the differentiation of clusters with ART-sensitive or ART-resistant cell lines (P = 0.00017). For exemplary validation, cell lines transduced with 3 of the 12 genes were used to prove a causative relationship. The cDNAs for a deletion-mutated epidermal growth factor receptor (EGFR) and for gamma-glutamylcysteine synthetase increased resistance to ART. The conditional expression of the CDC25A gene using a tetracycline repressor expression vector increased sensitivity toward ART. Multidrug-resistant cells differentially expressing the MDR1, MRP1, or BCRP genes were not cross-resistant to ART. ART acts via p53-dependent and- independent pathways in isogenic p53+/+ p21WAF1/CIP1+/+, p53-/- p21WAF1/CIP1+/+, and p53+/+ p21WAF1/CIP1-/- colon carcinoma cells.
Autoren
  • Thomas Efferth
  • Axel Sauerbrey
  • Armin Olbrich
  • Erich Gebhart
  • Pia Rauch
  • H Oliver Weber
  • Jan G Hengstler
  • Marc-Eric Halatsch
  • Manfred Volm
  • Kenneth D Tew
  • Douglas D Ross
  • Jens Oliver Funk
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/12869643
DOI
10.1124/mol.64.2.382
Funding acknowledgements
  • NCI NIH HHS: R01-CA77545
ISSN
0026-895X
Ausgabe der Veröffentlichung
2
Zeitschrift
Mol Pharmacol
Schlüsselwörter
  • Animals
  • Antineoplastic Agents
  • Apoptosis
  • Artemisinins
  • Artesunate
  • Cell Cycle
  • Cell Division
  • Cell Line, Transformed
  • Drug Resistance, Multiple
  • Drug Screening Assays, Antitumor
  • Gene Expression Profiling
  • HL-60 Cells
  • Humans
  • RNA, Messenger
  • Sesquiterpenes
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53
Sprache
eng
Country
United States
Paginierung
382 - 394
PII
64/2/382
Datum der Veröffentlichung
2003
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2003
Titel
Molecular modes of action of artesunate in tumor cell lines.
Sub types
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
Ausgabe der Zeitschrift
64

Datenquelle: PubMed

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