Willmar Schwabe Award 2006: Antiplasmodial and antitumor activity of arternisinin - From bench to bedside

Publication type:
Journal article
Metadata:
Autoren
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000246690600001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1055/s-2007-967138
eISSN
1439-0221
Externe Identifier
  • Clarivate Analytics Document Solution ID: 170UK
  • PubMed Identifier: 17354163
ISSN
0032-0943
Ausgabe der Veröffentlichung
4
Zeitschrift
PLANTA MEDICA
Schlüsselwörter
  • angiogenesis
  • apoptosis
  • artemisinin
  • artesunate
  • cluster analysis
  • comparative genomic hybridization
  • microarrays
  • oxidative stess
  • pharmacogenomics
Paginierung
299 - 309
Datum der Veröffentlichung
2007
Status
Published
Titel
Willmar Schwabe Award 2006: Antiplasmodial and antitumor activity of arternisinin - From bench to bedside
Sub types
  • Review
Ausgabe der Zeitschrift
73

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Thomas Efferth
DOI
10.1055/s-2007-967138
eISSN
1439-0221
ISSN
0032-0943
Ausgabe der Veröffentlichung
4
Zeitschrift
Planta Medica
Sprache
en
Paginierung
299 - 309
Datum der Veröffentlichung
2007
Status
Published
Herausgeber
Georg Thieme Verlag KG
Herausgeber URL
http://dx.doi.org/10.1055/s-2007-967138
Datum der Datenerfassung
2017
Titel
Willmar Schwabe Award 2006: Antiplasmodial and Antitumor Activity of Artemisinin - From Bench to Bedside
Ausgabe der Zeitschrift
73

Data source: Crossref

Abstract
Secondary metabolites from plants serve as defense against herbivores, microbes, viruses, or competing plants. Many medicinal plants have pharmacological activities and may, thus, be a source for novel treatment strategies. During the past 10 years, we have systematically analyzed medicinal plants used in traditional Chinese medicine and focused our interest on Artemisia annua L. (qinhao, sweet wormwood). We found that the active principle of Artemisia annua L., artemisinin, exerts not only antimalarial activity but also profound cytotoxicity against tumor cells. The inhibitory activity of artemisinin and its derivatives towards cancer cells is in the nano- to micromolar range. Candidate genes that may contribute to the sensitivity and resistance of tumor cells to artemisinins were identified by pharmacogenomic and molecular pharmacological approaches. Target validation was performed using cell lines transfected with candidate genes or corresponding knockout cells. The identified genes are from classes with diverse biological functions; for example, regulation of proliferation (BUB3, cyclins, CDC25A), angiogenesis (vascular endothelial growth factor and its receptor, matrix metalloproteinase-9, angiostatin, thrombospondin-1) or apoptosis (BCL-2, BAX, NF-kappaB). Artesunate triggers apoptosis both by p53-dependent and -independent pathways. Antioxidant stress genes (thioredoxin, catalase, gamma-glutamylcysteine synthetase, glutathione S-transferases) as well as the epidermal growth factor receptor confer resistance to artesunate. Cell lines overexpressing genes that confer resistance to established antitumor drugs (MDR1, MRP1, BCRP, dihydrofolate reductase, ribonucleotide reductase) were not cross-resistant to artesunate, indicating that artesunate is not involved in multidrug resistance. The anticancer activity of artesunate has also been shown in human xenograft tumors in mice. First encouraging experience in the clinical treatment of patients suffering from uveal melanoma calls for comprehensive clinical trials with artesunate for cancer treatment in the near future.
Addresses
  • German Cancer Research Center, Heidelberg, Germany. t.efferth@dkfz.de
Autoren
DOI
10.1055/s-2007-967138
eISSN
1439-0221
Externe Identifier
  • PubMed Identifier: 17354163
Open access
false
ISSN
0032-0943
Ausgabe der Veröffentlichung
4
Zeitschrift
Planta medica
Schlüsselwörter
  • Animals
  • Humans
  • Artemisia annua
  • Disease Models, Animal
  • Sesquiterpenes
  • Artemisinins
  • Antineoplastic Agents, Phytogenic
  • Antimalarials
  • Phytotherapy
  • Pharmacogenetics
  • Drug Resistance, Multiple
  • Awards and Prizes
Sprache
eng
Medium
Print-Electronic
Online publication date
2007
Paginierung
299 - 309
Datum der Veröffentlichung
2007
Status
Published
Datum der Datenerfassung
2007
Titel
Willmar Schwabe Award 2006: antiplasmodial and antitumor activity of artemisinin--from bench to bedside.
Sub types
  • Review
  • Journal Article
Ausgabe der Zeitschrift
73

Data source: Europe PubMed Central

Abstract
Secondary metabolites from plants serve as defense against herbivores, microbes, viruses, or competing plants. Many medicinal plants have pharmacological activities and may, thus, be a source for novel treatment strategies. During the past 10 years, we have systematically analyzed medicinal plants used in traditional Chinese medicine and focused our interest on Artemisia annua L. (qinhao, sweet wormwood). We found that the active principle of Artemisia annua L., artemisinin, exerts not only antimalarial activity but also profound cytotoxicity against tumor cells. The inhibitory activity of artemisinin and its derivatives towards cancer cells is in the nano- to micromolar range. Candidate genes that may contribute to the sensitivity and resistance of tumor cells to artemisinins were identified by pharmacogenomic and molecular pharmacological approaches. Target validation was performed using cell lines transfected with candidate genes or corresponding knockout cells. The identified genes are from classes with diverse biological functions; for example, regulation of proliferation (BUB3, cyclins, CDC25A), angiogenesis (vascular endothelial growth factor and its receptor, matrix metalloproteinase-9, angiostatin, thrombospondin-1) or apoptosis (BCL-2, BAX, NF-kappaB). Artesunate triggers apoptosis both by p53-dependent and -independent pathways. Antioxidant stress genes (thioredoxin, catalase, gamma-glutamylcysteine synthetase, glutathione S-transferases) as well as the epidermal growth factor receptor confer resistance to artesunate. Cell lines overexpressing genes that confer resistance to established antitumor drugs (MDR1, MRP1, BCRP, dihydrofolate reductase, ribonucleotide reductase) were not cross-resistant to artesunate, indicating that artesunate is not involved in multidrug resistance. The anticancer activity of artesunate has also been shown in human xenograft tumors in mice. First encouraging experience in the clinical treatment of patients suffering from uveal melanoma calls for comprehensive clinical trials with artesunate for cancer treatment in the near future.
Autoren
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/17354163
DOI
10.1055/s-2007-967138
ISSN
0032-0943
Ausgabe der Veröffentlichung
4
Zeitschrift
Planta Med
Schlüsselwörter
  • Animals
  • Antimalarials
  • Antineoplastic Agents, Phytogenic
  • Artemisia annua
  • Artemisinins
  • Awards and Prizes
  • Disease Models, Animal
  • Drug Resistance, Multiple
  • Humans
  • Pharmacogenetics
  • Phytotherapy
  • Sesquiterpenes
Sprache
eng
Country
Germany
Paginierung
299 - 309
Datum der Veröffentlichung
2007
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2007
Titel
Willmar Schwabe Award 2006: antiplasmodial and antitumor activity of artemisinin--from bench to bedside.
Sub types
  • Journal Article
  • Review
Ausgabe der Zeitschrift
73

Data source: PubMed

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