Treatment of Multidrug-Resistant Leukemia Cells by Novel Artemisinin-, Egonol-, and Thymoquinone-Derived Hybrid Compounds
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Lisa Gruber
- Sara Abdelfatah
- Tony Froehlich
- Christoph Reiter
- Volker Klein
- Svetlana B Tsogoeva
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000434717300133&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3390/molecules23040841
- eISSN
- 1420-3049
- Externe Identifier
- Clarivate Analytics Document Solution ID: GI7YB
- PubMed Identifier: 29642419
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- MOLECULES
- Schlüsselwörter
- chemotherapy
- multi-drug resistance
- artemisinin
- egonol
- thymoquinone
- hybrids
- Artikelnummer
- ARTN 841
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Titel
- Treatment of Multidrug-Resistant Leukemia Cells by Novel Artemisinin-, Egonol-, and Thymoquinone-Derived Hybrid Compounds
- Sub types
- Article
- Ausgabe der Zeitschrift
- 23
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Lisa Gruber
- Sara Abdelfatah
- Tony Fröhlich
- Christoph Reiter
- Volker Klein
- Svetlana Tsogoeva
- Thomas Efferth
- DOI
- 10.3390/molecules23040841
- eISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Molecules
- Sprache
- en
- Online publication date
- 2018
- Paginierung
- 841 - 841
- Status
- Published online
- Herausgeber
- MDPI AG
- Herausgeber URL
- http://dx.doi.org/10.3390/molecules23040841
- Datum der Datenerfassung
- 2018
- Titel
- Treatment of Multidrug-Resistant Leukemia Cells by Novel Artemisinin-, Egonol-, and Thymoquinone-Derived Hybrid Compounds
- Ausgabe der Zeitschrift
- 23
Data source: Crossref
- Abstract
- Two major obstacles for successful cancer treatment are the toxicity of cytostatics and the development of drug resistance in cancer cells during chemotherapy. Acquired or intrinsic drug resistance is responsible for almost 90% of treatment failure. For this reason, there is an urgent need for new anticancer drugs with improved efficacy against cancer cells, and with less toxicity on normal cells. There are impressive examples demonstrating the success of natural plant compounds to fight cancer, such as <i>Vinca</i> alkaloids, taxanes, and anthracyclines. Artesunic acid (ARTA), a drug for malaria treatment, also exerts cytotoxic activity towards cancer cells. Multidrug resistance often results from drug efflux pumps (ABC-transporters) that reduce intracellular drug levels. Hence, it would be interesting to know, whether ARTA could overcome drug resistance of tumor cells, and in what way ABC-transporters are involved. Different derivatives showing improved features concerning cytotoxicity and pharmacokinetic behavior have been developed. Considering both drug sensitivity and resistance, we chose a sensitive and a doxorubicin-resistant leukemia cell line and determined the killing effect of ARTA on these cells. Molecular docking and doxorubicin efflux assays were performed to investigate the interaction of the derivatives with <i>P</i>-glycoprotein. Using single-cell gel electrophoresis (alkaline comet assay), we showed that the derivatives of ARTA induce DNA breakage and accordingly programmed cell death, which represents a promising strategy in cancer treatment. ARTA activated apoptosis in cancer cells by the iron-mediated generation of reactive oxygen species (ROS). In conclusion, ARTA derivatives may bear the potential to be further developed as anticancer drugs.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, 55128 Mainz, Germany. gruber.lisa@googlemail.com.
- Autoren
- Lisa Gruber
- Sara Abdelfatah
- Tony Fröhlich
- Christoph Reiter
- Volker Klein
- Svetlana B Tsogoeva
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.3390/molecules23040841
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Identifier: 29642419
- PubMed Central ID: PMC6017613
- Open access
- true
- ISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Molecules (Basel, Switzerland)
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Leukemia
- Succinates
- Artemisinins
- Benzoquinones
- Doxorubicin
- ATP-Binding Cassette Transporters
- Antineoplastic Agents
- Drug Resistance, Multiple
- Cell Proliferation
- Cell Survival
- Gene Expression Regulation, Neoplastic
- Drug Resistance, Neoplasm
- Molecular Docking Simulation
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2018
- Open access status
- Open Access
- Paginierung
- E841
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2018
- Titel
- Treatment of Multidrug-Resistant Leukemia Cells by Novel Artemisinin-, Egonol-, and Thymoquinone-Derived Hybrid Compounds.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 23
Files
https://www.mdpi.com/1420-3049/23/4/841/pdf https://europepmc.org/articles/PMC6017613?pdf=render
Data source: Europe PubMed Central
- Abstract
- Two major obstacles for successful cancer treatment are the toxicity of cytostatics and the development of drug resistance in cancer cells during chemotherapy. Acquired or intrinsic drug resistance is responsible for almost 90% of treatment failure. For this reason, there is an urgent need for new anticancer drugs with improved efficacy against cancer cells, and with less toxicity on normal cells. There are impressive examples demonstrating the success of natural plant compounds to fight cancer, such as Vinca alkaloids, taxanes, and anthracyclines. Artesunic acid (ARTA), a drug for malaria treatment, also exerts cytotoxic activity towards cancer cells. Multidrug resistance often results from drug efflux pumps (ABC-transporters) that reduce intracellular drug levels. Hence, it would be interesting to know, whether ARTA could overcome drug resistance of tumor cells, and in what way ABC-transporters are involved. Different derivatives showing improved features concerning cytotoxicity and pharmacokinetic behavior have been developed. Considering both drug sensitivity and resistance, we chose a sensitive and a doxorubicin-resistant leukemia cell line and determined the killing effect of ARTA on these cells. Molecular docking and doxorubicin efflux assays were performed to investigate the interaction of the derivatives with P-glycoprotein. Using single-cell gel electrophoresis (alkaline comet assay), we showed that the derivatives of ARTA induce DNA breakage and accordingly programmed cell death, which represents a promising strategy in cancer treatment. ARTA activated apoptosis in cancer cells by the iron-mediated generation of reactive oxygen species (ROS). In conclusion, ARTA derivatives may bear the potential to be further developed as anticancer drugs.
- Date of acceptance
- 2018
- Autoren
- Lisa Gruber
- Sara Abdelfatah
- Tony Fröhlich
- Christoph Reiter
- Volker Klein
- Svetlana B Tsogoeva
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/29642419
- DOI
- 10.3390/molecules23040841
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Central ID: PMC6017613
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Molecules
- Schlüsselwörter
- artemisinin, egonol, thymoquinone, hybrids
- chemotherapy
- multi-drug resistance
- ATP-Binding Cassette Transporters
- Antineoplastic Agents
- Artemisinins
- Benzoquinones
- Cell Line, Tumor
- Cell Proliferation
- Cell Survival
- Doxorubicin
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- Gene Expression Regulation, Neoplastic
- Humans
- Leukemia
- Molecular Docking Simulation
- Succinates
- Sprache
- eng
- Country
- Switzerland
- PII
- molecules23040841
- Datum der Veröffentlichung
- 2018
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2018
- Titel
- Treatment of Multidrug-Resistant Leukemia Cells by Novel Artemisinin-, Egonol-, and Thymoquinone-Derived Hybrid Compounds.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 23
Data source: PubMed
- Beziehungen:
- Property of