Integration of Different "-omics" Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Benjamin Wiench
- Yet-Ran Chen
- Malte Paulsen
- Rebecca Hamm
- Sven Schroeder
- Ning-Sun Yang
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000321433000001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1155/2013/818709
- eISSN
- 1741-4288
- Externe Identifier
- Clarivate Analytics Document Solution ID: 178GI
- PubMed Identifier: 23861714
- ISSN
- 1741-427X
- Zeitschrift
- EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
- Artikelnummer
- ARTN 818709
- Datum der Veröffentlichung
- 2013
- Status
- Published
- Titel
- Integration of Different "-omics" Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 2013
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:p>Hematological malignancies frequently have a poor prognosis and often remain incurable. Drug resistance, severe side effects, and relapse are major problems of currently used drugs, and new candidate compounds are required for improvement of therapy success. The naphthoquinone shikonin derived from the Chinese medicinal herb,<jats:italic>Lithospermum erythrorhizon</jats:italic>, is a promising candidate for the next generation of chemotherapy. The basal cellular mechanism of shikonin is the direct targeting of mitochondria. Cytotoxicity screenings showed that the compound is particularly effective against leukemia cells suggesting an additional cellular mechanism. mRNA and miRNA microarrays were used to analyze changes in gene expression in leukemia cells after shikonin treatment and combined with stable-isotope dimethyl labeling for quantitative proteomics. The integration of bioinformatics and the three “-omics” assays showed that the PI3K-Akt-mTOR pathway was affected by shikonin. Deregulations of this pathway are frequently associated with cancerogenesis, especially in a wide range of hematological malignancies. The effect on the PI3K-Akt-mTOR axis was validated by demonstrating a decreased phosphorylation of Akt and a direct inhibition of the IGF1R kinase activity after shikonin treatment. Our results indicate that inhibiting the IGF1R-Akt-mTOR signaling cascade is a new cellular mechanism of shikonin strengthening its potential for the treatment of hematological malignancies.</jats:p>
- Autoren
- Benjamin Wiench
- Yet-Ran Chen
- Malte Paulsen
- Rebecca Hamm
- Sven Schröder
- Ning-Sun Yang
- Thomas Efferth
- DOI
- 10.1155/2013/818709
- eISSN
- 1741-4288
- ISSN
- 1741-427X
- Zeitschrift
- Evidence-Based Complementary and Alternative Medicine
- Sprache
- en
- Paginierung
- 1 - 11
- Datum der Veröffentlichung
- 2013
- Status
- Published
- Herausgeber
- Hindawi Limited
- Herausgeber URL
- http://dx.doi.org/10.1155/2013/818709
- Datum der Datenerfassung
- 2020
- Titel
- Integration of Different “-omics” Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells
- Ausgabe der Zeitschrift
- 2013
Data source: Crossref
- Abstract
- Hematological malignancies frequently have a poor prognosis and often remain incurable. Drug resistance, severe side effects, and relapse are major problems of currently used drugs, and new candidate compounds are required for improvement of therapy success. The naphthoquinone shikonin derived from the Chinese medicinal herb, Lithospermum erythrorhizon, is a promising candidate for the next generation of chemotherapy. The basal cellular mechanism of shikonin is the direct targeting of mitochondria. Cytotoxicity screenings showed that the compound is particularly effective against leukemia cells suggesting an additional cellular mechanism. mRNA and miRNA microarrays were used to analyze changes in gene expression in leukemia cells after shikonin treatment and combined with stable-isotope dimethyl labeling for quantitative proteomics. The integration of bioinformatics and the three "-omics" assays showed that the PI3K-Akt-mTOR pathway was affected by shikonin. Deregulations of this pathway are frequently associated with cancerogenesis, especially in a wide range of hematological malignancies. The effect on the PI3K-Akt-mTOR axis was validated by demonstrating a decreased phosphorylation of Akt and a direct inhibition of the IGF1R kinase activity after shikonin treatment. Our results indicate that inhibiting the IGF1R-Akt-mTOR signaling cascade is a new cellular mechanism of shikonin strengthening its potential for the treatment of hematological malignancies.
- Addresses
- Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
- Autoren
- Benjamin Wiench
- Yet-Ran Chen
- Malte Paulsen
- Rebecca Hamm
- Sven Schröder
- Ning-Sun Yang
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.1155/2013/818709
- eISSN
- 1741-4288
- Externe Identifier
- PubMed Identifier: 23861714
- PubMed Central ID: PMC3703888
- Funding acknowledgements
- Landesstiftung Rheinland-Pfalz:
- Open access
- true
- ISSN
- 1741-427X
- Zeitschrift
- Evidence-based complementary and alternative medicine : eCAM
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2013
- Open access status
- Open Access
- Paginierung
- 818709
- Datum der Veröffentlichung
- 2013
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2013
- Titel
- Integration of Different "-omics" Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 2013
Files
https://downloads.hindawi.com/journals/ecam/2013/818709.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23861714/pdf/?tool=EBI https://europepmc.org/articles/PMC3703888?pdf=render
Data source: Europe PubMed Central
- Abstract
- Hematological malignancies frequently have a poor prognosis and often remain incurable. Drug resistance, severe side effects, and relapse are major problems of currently used drugs, and new candidate compounds are required for improvement of therapy success. The naphthoquinone shikonin derived from the Chinese medicinal herb, Lithospermum erythrorhizon, is a promising candidate for the next generation of chemotherapy. The basal cellular mechanism of shikonin is the direct targeting of mitochondria. Cytotoxicity screenings showed that the compound is particularly effective against leukemia cells suggesting an additional cellular mechanism. mRNA and miRNA microarrays were used to analyze changes in gene expression in leukemia cells after shikonin treatment and combined with stable-isotope dimethyl labeling for quantitative proteomics. The integration of bioinformatics and the three "-omics" assays showed that the PI3K-Akt-mTOR pathway was affected by shikonin. Deregulations of this pathway are frequently associated with cancerogenesis, especially in a wide range of hematological malignancies. The effect on the PI3K-Akt-mTOR axis was validated by demonstrating a decreased phosphorylation of Akt and a direct inhibition of the IGF1R kinase activity after shikonin treatment. Our results indicate that inhibiting the IGF1R-Akt-mTOR signaling cascade is a new cellular mechanism of shikonin strengthening its potential for the treatment of hematological malignancies.
- Date of acceptance
- 2013
- Autoren
- Benjamin Wiench
- Yet-Ran Chen
- Malte Paulsen
- Rebecca Hamm
- Sven Schröder
- Ning-Sun Yang
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/23861714
- DOI
- 10.1155/2013/818709
- Externe Identifier
- PubMed Central ID: PMC3703888
- ISSN
- 1741-427X
- Zeitschrift
- Evid Based Complement Alternat Med
- Sprache
- eng
- Country
- United States
- Paginierung
- 818709
- Datum der Veröffentlichung
- 2013
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2013
- Titel
- Integration of Different "-omics" Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 2013
Data source: PubMed
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