Gene expression profiling identifies novel key players involved in the cytotoxic effect of Artesunate on pancreatic cancer cells
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Mahmoud Youns
- Thomas Efferth
- Juergen Reichling
- Kurt Fellenberg
- Andrea Bauer
- Joerg D Hoheisel
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000266902300008&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.bcp.2009.04.014
- Externe Identifier
- Clarivate Analytics Document Solution ID: 457CF
- PubMed Identifier: 19393226
- ISSN
- 0006-2952
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- BIOCHEMICAL PHARMACOLOGY
- Schlüsselwörter
- Artesunate
- Pancreatic cancer
- Microarray
- Topoisomerase
- Ingenuity Pathway Analysis
- Paginierung
- 273 - 283
- Datum der Veröffentlichung
- 2009
- Status
- Published
- Titel
- Gene expression profiling identifies novel key players involved in the cytotoxic effect of Artesunate on pancreatic cancer cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 78
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Mahmoud Youns
- Thomas Efferth
- Jürgen Reichling
- Kurt Fellenberg
- Andrea Bauer
- Jörg D Hoheisel
- DOI
- 10.1016/j.bcp.2009.04.014
- ISSN
- 0006-2952
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Biochemical Pharmacology
- Sprache
- en
- Paginierung
- 273 - 283
- Datum der Veröffentlichung
- 2009
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.bcp.2009.04.014
- Datum der Datenerfassung
- 2019
- Titel
- Gene expression profiling identifies novel key players involved in the cytotoxic effect of Artesunate on pancreatic cancer cells
- Ausgabe der Zeitschrift
- 78
Data source: Crossref
- Abstract
- Pancreatic cancer is one of the most aggressive human malignancies, with an extremely poor prognosis. The paucity of curative therapies has translated into an overall 5-year survival rate of less than 5%, underscoring a desperate need for new therapeutic options. Artesunate (ART), clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity. However, the mechanisms underlying those activities in pancreatic cancer are not yet known. Here we evaluated the anti-tumor activity of Artesunate and the possible underlying mechanisms in pancreatic cancer. MiaPaCa-2 (poorly differentiated) and BxPC-3 (moderately differentiated) pancreatic cancer cell lines were treated with Artesunate and the effect was monitored by a tetrazolium-based assay (MTS) for evaluating cell viability and by flow cytometry and caspase 3/7 activation for apoptosis evaluation. In addition cDNA arrays were used to identify differentially expressed genes. The microarray data were then validated by RT-PCR and Western blotting. Moreover, pathways associated with these expression changes were identified using the Ingenuity Pathway Analysis. The expression analysis identified a common set of genes that were regulated by Artesunate in pancreatic cancer. Our results provide the first in vitro evidence for the therapeutic utility of Artesunate in pancreatic cancer. Moreover, we identified Artesunate as a novel topoisomerase IIalpha inhibitor that inhibits pancreatic cancer growth through modulation of multiple signaling pathways. 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 Artesunate in tumor cells.
- Addresses
- Department of Functional Genome Analysis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. m.youns@dkfz.de
- Autoren
- Mahmoud Youns
- Thomas Efferth
- Thomas Efferth
- Jürgen Reichling
- Kurt Fellenberg
- Andrea Bauer
- Jörg D Hoheisel
- DOI
- 10.1016/j.bcp.2009.04.014
- eISSN
- 1873-2968
- Externe Identifier
- PubMed Identifier: 19393226
- Open access
- false
- ISSN
- 0006-2952
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Biochemical pharmacology
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Pancreatic Neoplasms
- Artemisinins
- Antineoplastic Agents
- Oligonucleotide Array Sequence Analysis
- Flow Cytometry
- Gene Expression Profiling
- Reverse Transcriptase Polymerase Chain Reaction
- Apoptosis
- Dose-Response Relationship, Drug
- Artesunate
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2009
- Paginierung
- 273 - 283
- Datum der Veröffentlichung
- 2009
- Status
- Published
- Datum der Datenerfassung
- 2009
- Titel
- Gene expression profiling identifies novel key players involved in the cytotoxic effect of Artesunate on pancreatic cancer cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 78
Data source: Europe PubMed Central
- Abstract
- Pancreatic cancer is one of the most aggressive human malignancies, with an extremely poor prognosis. The paucity of curative therapies has translated into an overall 5-year survival rate of less than 5%, underscoring a desperate need for new therapeutic options. Artesunate (ART), clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity. However, the mechanisms underlying those activities in pancreatic cancer are not yet known. Here we evaluated the anti-tumor activity of Artesunate and the possible underlying mechanisms in pancreatic cancer. MiaPaCa-2 (poorly differentiated) and BxPC-3 (moderately differentiated) pancreatic cancer cell lines were treated with Artesunate and the effect was monitored by a tetrazolium-based assay (MTS) for evaluating cell viability and by flow cytometry and caspase 3/7 activation for apoptosis evaluation. In addition cDNA arrays were used to identify differentially expressed genes. The microarray data were then validated by RT-PCR and Western blotting. Moreover, pathways associated with these expression changes were identified using the Ingenuity Pathway Analysis. The expression analysis identified a common set of genes that were regulated by Artesunate in pancreatic cancer. Our results provide the first in vitro evidence for the therapeutic utility of Artesunate in pancreatic cancer. Moreover, we identified Artesunate as a novel topoisomerase IIalpha inhibitor that inhibits pancreatic cancer growth through modulation of multiple signaling pathways. 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 Artesunate in tumor cells.
- Date of acceptance
- 2009
- Autoren
- Mahmoud Youns
- Thomas Efferth
- Jürgen Reichling
- Kurt Fellenberg
- Andrea Bauer
- Jörg D Hoheisel
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/19393226
- DOI
- 10.1016/j.bcp.2009.04.014
- eISSN
- 1873-2968
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Biochem Pharmacol
- Schlüsselwörter
- Antineoplastic Agents
- Apoptosis
- Artemisinins
- Artesunate
- Cell Line, Tumor
- Dose-Response Relationship, Drug
- Flow Cytometry
- Gene Expression Profiling
- Humans
- Oligonucleotide Array Sequence Analysis
- Pancreatic Neoplasms
- Reverse Transcriptase Polymerase Chain Reaction
- Sprache
- eng
- Country
- England
- Paginierung
- 273 - 283
- PII
- S0006-2952(09)00298-6
- Datum der Veröffentlichung
- 2009
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2009
- Titel
- Gene expression profiling identifies novel key players involved in the cytotoxic effect of Artesunate on pancreatic cancer cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 78
Data source: PubMed
- Beziehungen:
- Property of