Integration of Different “-omics” Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells
Joint Authors
Hamm, Rebecca
Paulsen, Malte
Efferth, Thomas
Schroeder, Sven
Chen, Yet-Ran
Wiench, Benjamin
Yang, Ning-Sun
Source
Evidence-Based Complementary and Alternative Medicine
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-06-19
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Wiench, Benjamin& Chen, Yet-Ran& Paulsen, Malte& Hamm, Rebecca& Schroeder, Sven& Yang, Ning-Sun…[et al.]. 2013. Integration of Different “-omics” Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells. Evidence-Based Complementary and Alternative Medicine،Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-500602
Modern Language Association (MLA)
Wiench, Benjamin…[et al.]. Integration of Different “-omics” Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells. Evidence-Based Complementary and Alternative Medicine No. 2013 (2013), pp.1-11.
https://search.emarefa.net/detail/BIM-500602
American Medical Association (AMA)
Wiench, Benjamin& Chen, Yet-Ran& Paulsen, Malte& Hamm, Rebecca& Schroeder, Sven& Yang, Ning-Sun…[et al.]. Integration of Different “-omics” Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells. Evidence-Based Complementary and Alternative Medicine. 2013. Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-500602
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-500602