Therapeutic implication of ‘Iturin A’ for targeting MD-2/TLR4 complex to overcome angiogenesis and invasion
| Autor: | Aditya Parekh, Goutam Dey, Ramkrishna Sen, Payel Banik, Mahitosh Mandal, Rashmi Bharti, Indranil Banerjee, Ipsita Pal, Sheetal Parida, Y. Rajesh, Probir Kumar Ojha |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Receptor complex Angiogenesis Lymphocyte Antigen 96 Biology Matrix metalloproteinase Peptides Cyclic 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Western blot Cell Line Tumor Neoplasms Human Umbilical Vein Endothelial Cells medicine Humans Neoplasm Invasiveness RNA Small Interfering Matrigel Neovascularization Pathologic medicine.diagnostic_test NF-kappa B NF-κB Cell Biology In vitro I-kappa B Kinase Gene Expression Regulation Neoplastic Toll-Like Receptor 4 030104 developmental biology chemistry 030220 oncology & carcinogenesis Myeloid Differentiation Factor 88 Immunology Bacillus megaterium Cancer research Signal transduction Signal Transduction |
| Zdroj: | Cellular Signalling. 35:24-36 |
| ISSN: | 0898-6568 |
| Popis: | Tumor angiogenesis and invasion are deregulated biological processes that drive multistage transformation of tumors from a benign to a life-threatening malignant state activating multiple signaling pathways including MD-2/TLR4/NF-κB. Development of potential inhibitors of this signaling is emerging area for discovery of novel cancer therapeutics. In the current investigation, we identified Iturin A (A lipopeptide molecule from Bacillus megaterium) as a potent inhibitor of angiogenesis and cancer invasion by various in vitro and in vivo methods. Iturin A was found to suppress VEGF, a powerful inducer of angiogenesis and key player in tumor invasion, as confirmed by ELISA, western blot and real time PCR. Iturin A inhibited endothelial tube arrangement, blood capillary formation, endothelial sprouting and vascular growth inside the matrigel. In addition, Iturin A inhibited MMP-2/9 expression in MDA-MB-231 and HUVEC cells. Cancer invasion, migration and colony forming ability were significantly hampered by Iturin A. Expressions of MD-2/TLR4 and its downstream MyD88, IKK-α and NF-κB were also reduced in treated MDA-MB-231 and HUVEC cells. Western blot and immunofluorescence study showed that nuclear accumulation of NF-κB was hampered by Iturin A. MD-2 siRNA or plasmid further confirmed the efficacy of Iturin A by suppressing MD-2/TLR4 signaling pathway. The in silico docking study showed that the Iturin A interacted well with the MD-2 in MD-2/TLR4 receptor complex. Conclusively, inhibition of MD-2/TLR4 complex with Iturin A offered strategic advancement in cancer therapy. |
| Databáze: | OpenAIRE |
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