mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether

Publication type:
Journal article
Metadata:
Autoren
  • T Efferth
  • A Olbrich
  • R Bauer
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000177778000007&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/S0006-2952(02)01221-2
Externe Identifier
  • Clarivate Analytics Document Solution ID: 589UD
  • PubMed Identifier: 12167480
ISSN
0006-2952
Ausgabe der Veröffentlichung
4
Zeitschrift
BIOCHEMICAL PHARMACOLOGY
Schlüsselwörter
  • chemotherapy
  • microarray analysis
  • hierarchical cluster analysis
Artikelnummer
PII S0006-2952(02)01221-2
Paginierung
617 - 623
Datum der Veröffentlichung
2002
Status
Published
Titel
mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether
Sub types
  • Article
Ausgabe der Zeitschrift
64

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Thomas Efferth
  • Armin Olbrich
  • Rudolf Bauer
DOI
10.1016/s0006-2952(02)01221-2
ISSN
0006-2952
Ausgabe der Veröffentlichung
4
Zeitschrift
Biochemical Pharmacology
Sprache
en
Paginierung
617 - 623
Datum der Veröffentlichung
2002
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/s0006-2952(02)01221-2
Datum der Datenerfassung
2019
Titel
mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether
Ausgabe der Zeitschrift
64

Data source: Crossref

Abstract
The antimalarial artemisinin derivatives artesunate (ART), arteether (ARE), and artemether (ARM) reveal remarkable antineoplastic activity. In the present investigation, we identified mRNA expression profiles associated with the response of tumor cells to ART, ARE, and ARM. We performed correlation and hierarchical cluster analyses of inhibition concentration 50% (IC(50)) values and basal mRNA expression levels of 464 genes deposited in the database of the National Cancer Institute, USA. Correlating IC(50) values of ART, ARE, and ARM and of 16 established antineoplastic drugs revealed that the artemisinin derivatives could not be assigned with a known class of drugs with defined mode(s) of action. The basal mRNA expression of 208 out of 464 genes (45%) correlated significantly with IC(50) values of at least one artemisinin derivative. These genes were from different classes (drug resistance genes, DNA damage and repair genes, apoptosis-regulating genes, proliferation-associated genes, oncogenes, tumor suppressor genes and cytokines). We identified two different gene clusters by hierarchical cluster analysis. One cluster contained predominately genes significantly correlated to all three artemisinin derivatives. This overlapping set of genes points to common molecular mechanisms of tumor inhibition by all three drugs in which genes affecting cellular proliferation may play an important role. The second cluster contained genes differentially associated with the response of artemisinin derivatives to cancer cells. The number of correlating drug resistance genes in this cluster increased in the order ART<ARE<ARM and was paralleled by increasing IC(50) values of the three drugs in the same order. The higher activity of ART in comparison to ARE and ARM may, thus, be explained by a lower number of drug resistance genes affecting ARTs action. The present analysis is a starting point for the generation of hypotheses on candidate genes and for a more detailed dissection of the functional role of individual genes for the activity of artemisinin derivatives in tumor cells.
Addresses
  • Virtual Campus Rhineland-Palatinate, P.O. Box 4380, 55033 Mainz, Germany. efferth@vcrp.de
Autoren
DOI
10.1016/s0006-2952(02)01221-2
eISSN
1873-2968
Externe Identifier
  • PubMed Identifier: 12167480
Open access
false
ISSN
0006-2952
Ausgabe der Veröffentlichung
4
Zeitschrift
Biochemical pharmacology
Schlüsselwörter
  • Cell Line
  • Tumor Cells, Cultured
  • Humans
  • Sesquiterpenes
  • Artemisinins
  • RNA, Messenger
  • Antimalarials
  • Oligonucleotide Array Sequence Analysis
  • Gene Expression Profiling
  • Transcription, Genetic
  • Artesunate
  • Artemether
Sprache
eng
Medium
Print
Paginierung
617 - 623
Datum der Veröffentlichung
2002
Status
Published
Datum der Datenerfassung
2002
Titel
mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
64

Data source: Europe PubMed Central

Abstract
The antimalarial artemisinin derivatives artesunate (ART), arteether (ARE), and artemether (ARM) reveal remarkable antineoplastic activity. In the present investigation, we identified mRNA expression profiles associated with the response of tumor cells to ART, ARE, and ARM. We performed correlation and hierarchical cluster analyses of inhibition concentration 50% (IC(50)) values and basal mRNA expression levels of 464 genes deposited in the database of the National Cancer Institute, USA. Correlating IC(50) values of ART, ARE, and ARM and of 16 established antineoplastic drugs revealed that the artemisinin derivatives could not be assigned with a known class of drugs with defined mode(s) of action. The basal mRNA expression of 208 out of 464 genes (45%) correlated significantly with IC(50) values of at least one artemisinin derivative. These genes were from different classes (drug resistance genes, DNA damage and repair genes, apoptosis-regulating genes, proliferation-associated genes, oncogenes, tumor suppressor genes and cytokines). We identified two different gene clusters by hierarchical cluster analysis. One cluster contained predominately genes significantly correlated to all three artemisinin derivatives. This overlapping set of genes points to common molecular mechanisms of tumor inhibition by all three drugs in which genes affecting cellular proliferation may play an important role. The second cluster contained genes differentially associated with the response of artemisinin derivatives to cancer cells. The number of correlating drug resistance genes in this cluster increased in the order ART<ARE<ARM and was paralleled by increasing IC(50) values of the three drugs in the same order. The higher activity of ART in comparison to ARE and ARM may, thus, be explained by a lower number of drug resistance genes affecting ARTs action. The present analysis is a starting point for the generation of hypotheses on candidate genes and for a more detailed dissection of the functional role of individual genes for the activity of artemisinin derivatives in tumor cells.
Autoren
  • Thomas Efferth
  • Armin Olbrich
  • Rudolf Bauer
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/12167480
DOI
10.1016/s0006-2952(02)01221-2
ISSN
0006-2952
Ausgabe der Veröffentlichung
4
Zeitschrift
Biochem Pharmacol
Schlüsselwörter
  • Antimalarials
  • Artemether
  • Artemisinins
  • Artesunate
  • Cell Line
  • Gene Expression Profiling
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger
  • Sesquiterpenes
  • Transcription, Genetic
  • Tumor Cells, Cultured
Sprache
eng
Country
England
Paginierung
617 - 623
PII
S0006295202012212
Datum der Veröffentlichung
2002
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2002
Titel
mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
64

Data source: PubMed

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