Molecular modes of action of artesunate in tumor cell lines
- Publication type:
- Journal article
- Metadata:
-
- 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
Data source: Web of Science (Lite)
- Other metadata sources:
-
- 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
Data source: 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
- 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
Data source: 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
Data source: PubMed
- Beziehungen:
- Property of