Artesunate Induces ROS-Mediated Apoptosis in Doxorubicin-Resistant T Leukemia Cells
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Thomas Efferth
- Marco Giaisi
- Annette Merling
- Peter H Krammer
- Min Li-Weber
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000207452300028&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1371/journal.pone.0000693
- Externe Identifier
- Clarivate Analytics Document Solution ID: V10GK
- PubMed Identifier: 17668070
- ISSN
- 1932-6203
- Ausgabe der Veröffentlichung
- 8
- Zeitschrift
- PLOS ONE
- Artikelnummer
- ARTN e693
- Datum der Veröffentlichung
- 2007
- Status
- Published
- Titel
- Artesunate Induces ROS-Mediated Apoptosis in Doxorubicin-Resistant T Leukemia Cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 2
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Thomas Efferth
- Marco Giaisi
- Annette Merling
- Peter H Krammer
- Min Li-Weber
- DOI
- 10.1371/journal.pone.0000693
- Editoren
- Nils Cordes
- eISSN
- 1932-6203
- Ausgabe der Veröffentlichung
- 8
- Zeitschrift
- PLoS ONE
- Sprache
- en
- Online publication date
- 2007
- Paginierung
- e693 - e693
- Status
- Published online
- Herausgeber
- Public Library of Science (PLoS)
- Herausgeber URL
- http://dx.doi.org/10.1371/journal.pone.0000693
- Datum der Datenerfassung
- 2019
- Titel
- Artesunate Induces ROS-Mediated Apoptosis in Doxorubicin-Resistant T Leukemia Cells
- Ausgabe der Zeitschrift
- 2
Data source: Crossref
- Abstract
- <h4>Background</h4>A major obstacle for successful cancer treatment often is the development of drug resistance in cancer cells during chemotherapy. Therefore, there is an urgent need for novel drugs with improved efficacy against tumor cells and with less toxicity on normal cells. Artesunate (ART), a powerful anti-malarial herbal compound, has been shown to inhibit growth of various tumor cell lines in vitro and of xenografted Kaposi's sarcoma in mice in vivo. However, the molecular mechanisms by which ART exerts its cytotoxicity have not been elucidated. The ART-class of anti-malarial compounds is attractive due to their activity against multidrug-resistant Plasmodium falciparum and Plasmodium vivax strains. Another salient feature of these compounds is the lack of severe side effects in malaria patients.<h4>Methodology and principal findings</h4>In this study, we used T-cell leukemias as a model system to study the molecular mechanisms of ART-induced apoptosis. The most typical anticancer drugs are DNA intercalators such as Doxorubicin. To investigate drug sensitivity and resistance, we chose a Doxorubicin-resistant leukemia cell line and investigated the killing effect of ART on these cells. We show that ART induces apoptosis in leukemic T cells mainly through the mitochondrial pathway via generation of reactive oxygen species (ROS), a mechanism different from Doxorubicin. This is confirmed by the fact that the antioxidant N-Acetyle-Cysteine (NAC) could completely block ROS generation and, consequently, inhibited ART-induced apoptosis. Therefore, ART can overcome the Doxorubicin-resistance and induce the Doxorubicin-resistant leukemia cells to undergo apoptosis. We also show that ART can synergize with Doxorubicin to enhance apoptotic cell death in leukemic T cells. This synergistic effect can be largely explained by the fact that ART and Doxorubicin use different killing mechanisms.<h4>Conclusions</h4>Our studies raise the possibility to develop ART in combination with other established anticancer drugs which induce apoptosis through the pathways or mechanisms different from ART.
- Addresses
- Pharmaceutical Biology of Natural Products, German Cancer Research Center, Heidelberg, Germany.
- Autoren
- Thomas Efferth
- Thomas Efferth
- Marco Giaisi
- Annette Merling
- Peter H Krammer
- Min Li-Weber
- DOI
- 10.1371/journal.pone.0000693
- eISSN
- 1932-6203
- Externe Identifier
- PubMed Identifier: 17668070
- PubMed Central ID: PMC1933253
- Open access
- true
- ISSN
- 1932-6203
- Ausgabe der Veröffentlichung
- 8
- Zeitschrift
- PloS one
- Schlüsselwörter
- Cell Line, Tumor
- Animals
- Humans
- Mice
- Leukemia
- Reactive Oxygen Species
- Artemisinins
- Doxorubicin
- Acetylcysteine
- Antibiotics, Antineoplastic
- Free Radical Scavengers
- Antimalarials
- Drug Screening Assays, Antitumor
- Apoptosis
- Oxidation-Reduction
- Drug Resistance, Neoplasm
- Artesunate
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2007
- Open access status
- Open Access
- Paginierung
- e693
- Datum der Veröffentlichung
- 2007
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2007
- Titel
- Artesunate induces ROS-mediated apoptosis in doxorubicin-resistant T leukemia cells.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 2
Files
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000693&type=printable https://europepmc.org/articles/PMC1933253?pdf=render
Data source: Europe PubMed Central
- Abstract
- BACKGROUND: A major obstacle for successful cancer treatment often is the development of drug resistance in cancer cells during chemotherapy. Therefore, there is an urgent need for novel drugs with improved efficacy against tumor cells and with less toxicity on normal cells. Artesunate (ART), a powerful anti-malarial herbal compound, has been shown to inhibit growth of various tumor cell lines in vitro and of xenografted Kaposi's sarcoma in mice in vivo. However, the molecular mechanisms by which ART exerts its cytotoxicity have not been elucidated. The ART-class of anti-malarial compounds is attractive due to their activity against multidrug-resistant Plasmodium falciparum and Plasmodium vivax strains. Another salient feature of these compounds is the lack of severe side effects in malaria patients. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we used T-cell leukemias as a model system to study the molecular mechanisms of ART-induced apoptosis. The most typical anticancer drugs are DNA intercalators such as Doxorubicin. To investigate drug sensitivity and resistance, we chose a Doxorubicin-resistant leukemia cell line and investigated the killing effect of ART on these cells. We show that ART induces apoptosis in leukemic T cells mainly through the mitochondrial pathway via generation of reactive oxygen species (ROS), a mechanism different from Doxorubicin. This is confirmed by the fact that the antioxidant N-Acetyle-Cysteine (NAC) could completely block ROS generation and, consequently, inhibited ART-induced apoptosis. Therefore, ART can overcome the Doxorubicin-resistance and induce the Doxorubicin-resistant leukemia cells to undergo apoptosis. We also show that ART can synergize with Doxorubicin to enhance apoptotic cell death in leukemic T cells. This synergistic effect can be largely explained by the fact that ART and Doxorubicin use different killing mechanisms. CONCLUSIONS: Our studies raise the possibility to develop ART in combination with other established anticancer drugs which induce apoptosis through the pathways or mechanisms different from ART.
- Date of acceptance
- 2007
- Autoren
- Thomas Efferth
- Marco Giaisi
- Annette Merling
- Peter H Krammer
- Min Li-Weber
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/17668070
- DOI
- 10.1371/journal.pone.0000693
- eISSN
- 1932-6203
- Externe Identifier
- PubMed Central ID: PMC1933253
- Ausgabe der Veröffentlichung
- 8
- Zeitschrift
- PLoS One
- Schlüsselwörter
- Acetylcysteine
- Animals
- Antibiotics, Antineoplastic
- Antimalarials
- Apoptosis
- Artemisinins
- Artesunate
- Cell Line, Tumor
- Doxorubicin
- Drug Resistance, Neoplasm
- Drug Screening Assays, Antitumor
- Free Radical Scavengers
- Humans
- Leukemia
- Mice
- Oxidation-Reduction
- Reactive Oxygen Species
- Sprache
- eng
- Country
- United States
- Paginierung
- e693
- Datum der Veröffentlichung
- 2007
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2010
- Titel
- Artesunate induces ROS-mediated apoptosis in doxorubicin-resistant T leukemia cells.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 2
Data source: PubMed
- Beziehungen:
- Property of