The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling
| Autor: | Rascle, Anne, Michl, Carina, Vivarelli, Fabio, Weigl, Julia, De Nicola, Gina Rosalinda, Canistro, Donatella, Paolini, Moreno, Iori, Renato |
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| Přispěvatelé: | Michl, Carina, Vivarelli, Fabio, Weigl, Julia, De Nicola, Gina Rosalinda, Canistro, Donatella, Paolini, Moreno, Iori, Renato, Rascle, Anne |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Cell signaling
Cultured tumor cells 610 Medizin lcsh:Medicine Signal transduction Toxicology Pathology and Laboratory Medicine Biochemistry Mice Isothiocyanates Medicine and Health Sciences STAT5 Transcription Factor Post-Translational Modification Phosphorylation lcsh:Science Moringa oleifera ddc:610 Molecular Structure Reverse Transcriptase Polymerase Chain Reaction STAT signaling STAT proteins STAT Transcription Factors STAT1 Transcription Factor Cell Processes Seeds Cell lines Biological cultures Research Article Cell death Cell biology Signal Inhibition animal structures Cell Survival Blotting Western Cell Line Genetics Animals Humans HeLa cells Janus Kinases Dose-Response Relationship Drug Toxicity Precursor Cells B-Lymphoid lcsh:R NF-KAPPA-B JAK-STAT PATHWAY ENDOTHELIAL-CELLS TRANSCRIPTION 3 CANCER-CELLS IN-VIVO GLUCOMORINGIN ISOTHIOCYANATE DEACETYLASE INHIBITORS MONOCYTE ADHESION CHEMICAL BIOLOGY Biology and Life Sciences Proteins Interferon-alpha STAT2 Transcription Factor Cell cultures Research and analysis methods lcsh:Q Interleukin-3 Gene expression |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 6, p e0157430 (2016) |
| Popis: | Sulforaphane (SFN) and moringin (GMG-ITC) are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-kappa B. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFN alpha-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-kappa B activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders. |
| Databáze: | OpenAIRE |
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