Michl, Carina and Vivarelli, Fabio and Weigl, Julia and De Nicola, Gina Rosalinda and Canistro, Donatella and Paolini, Moreno and Iori, Renato and Rascle, Anne (2016) The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling. PLOS ONE, 11 (6): e0157430. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; JAK-STAT PATHWAY; ENDOTHELIAL-CELLS; TRANSCRIPTION 3; CANCER-CELLS; IN-VIVO; GLUCOMORINGIN ISOTHIOCYANATE; DEACETYLASE INHIBITORS; MONOCYTE ADHESION; CHEMICAL BIOLOGY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2019 08:25 |
| Last Modified: | 22 Mar 2019 08:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2766 |
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