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A natural product-like JAK2/STAT3 inhibitor induces apoptosis of malignant melanoma cells
- Source :
- PLoS ONE, PLoS ONE, Vol 12, Iss 6, p e0177123 (2017)
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- The JAK2/STAT3 signaling pathway plays a critical role in tumorigenesis, and has been suggested as a potential molecular target for anti-melanoma therapeutics. However, few JAK2 inhibitors were being tested for melanoma therapy. In this study, eight amentoflavone analogues were evaluated for their activity against human malignant melanoma cells. The most potent analogue, compound 1, inhibited the phosphorylation of JAK2 and STAT3 in human melanoma cells, but had no discernible effect on total JAK2 and STAT3 levels. A cellular thermal shift assay was performed to identify that JAK2 is engaged by 1 in cell lysates. Moreover, compound 1 showed higher antiproliferative activity against human melanoma A375 cells compared to a panel of cancer and normal cell lines. Compound 1 also activated caspase-3 and cleaved PARP, which are markers of apoptosis, and suppressed the anti-apoptotic Bcl-2 level. Finally, compound 1 induced apoptosis in 80% of treated melanoma cells. To our knowledge, compound 1 is the first amentoflavone-based JAK2 inhibitor to be investigated for use as an anti-melanoma agent.<br />published_or_final_version
- Subjects :
- Melanomas
0301 basic medicine
lcsh:Medicine
Apoptosis
Amentoflavone
medicine.disease_cause
Biochemistry
chemistry.chemical_compound
Spectrum Analysis Techniques
0302 clinical medicine
Cell Signaling
Medicine and Health Sciences
Enzyme assays
Colorimetric assays
Post-Translational Modification
Phosphorylation
lcsh:Science
STAT3
Bioassays and physiological analysis
Melanoma
Cultured Tumor Cells
MTT assay
Multidisciplinary
Cell Death
Flow Cytometry
STAT signaling
Oncology
UVB-induced apoptosis
Cell Processes
Spectrophotometry
030220 oncology & carcinogenesis
Melanoma Cells
Biological Cultures
Cytophotometry
Research Article
Signal Transduction
STAT3 Transcription Factor
Signal Inhibition
Biology
Research and Analysis Methods
03 medical and health sciences
Cell Line, Tumor
medicine
Humans
Biological Products
lcsh:R
Biology and Life Sciences
Cancers and Neoplasms
Proteins
Cell Biology
Cell Cultures
Janus Kinase 2
medicine.disease
Molecular biology
030104 developmental biology
chemistry
Cell culture
Biochemical analysis
biology.protein
lcsh:Q
Carcinogenesis
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....3b3001951583665847e538db12f81fa7