A Novel Quinoline Inhibitor of the Canonical NF-κB Transcription Factor Pathway
The NF-κB family of transcription factors is a master regulator of cellular responses during inflammation, and its dysregulation has been linked to chronic inflammatory diseases, such as inflammatory bowel disease. It is therefore of vital importance to design and test new effective NF-κB inhibitors...
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MDPI AG
2024-11-01
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| author | Panagiotis Ntavaroukas Konstantinos Michail Rafaela Tsiakalidou Eleni Stampouloglou Katerina Tsiggene Dimitrios Komiotis Nikitas Georgiou Thomas Mavromoustakos Stella Manta Danielle Aje Panagiotis Michael Barry J. Campbell Stamatia Papoutsopoulou |
| author_facet | Panagiotis Ntavaroukas Konstantinos Michail Rafaela Tsiakalidou Eleni Stampouloglou Katerina Tsiggene Dimitrios Komiotis Nikitas Georgiou Thomas Mavromoustakos Stella Manta Danielle Aje Panagiotis Michael Barry J. Campbell Stamatia Papoutsopoulou |
| author_sort | Panagiotis Ntavaroukas |
| collection | DOAJ |
| description | The NF-κB family of transcription factors is a master regulator of cellular responses during inflammation, and its dysregulation has been linked to chronic inflammatory diseases, such as inflammatory bowel disease. It is therefore of vital importance to design and test new effective NF-κB inhibitors that have the potential to be utilized in clinical practice. In this study, we used a commercial transgenic HeLa cell line as an NF-κB activation reporter to test a novel quinoline molecule, Q3, as a potential inhibitor of the canonical NF-κB pathway. Q3 inhibited NF-κB-induced luciferase in concentrations as low as 5 μM and did not interfere with cell survival or induced cell death. A real-time PCR analysis revealed that Q3 could inhibit the TNF-induced transcription of the luciferase gene, as well as the <i>TNF</i> gene, a known downstream target gene. Immunocytochemistry studies revealed that Q3 moderately interferes with TNF-induced NF-κB nuclear translocation. Moreover, docking and molecular dynamics analyses confirmed that Q3 could potentially modulate transcriptional activity by inhibiting the interaction of NF-κB and DNA. Therefore, Q3 could be potentially developed for further in vivo studies as an NF-κB inhibitor. |
| format | Article |
| id | doaj-art-0793f7f718f342bf93b61940f422f788 |
| institution | OA Journals |
| issn | 2079-7737 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj-art-0793f7f718f342bf93b61940f422f7882025-08-20T02:08:02ZengMDPI AGBiology2079-77372024-11-01131191010.3390/biology13110910A Novel Quinoline Inhibitor of the Canonical NF-κB Transcription Factor PathwayPanagiotis Ntavaroukas0Konstantinos Michail1Rafaela Tsiakalidou2Eleni Stampouloglou3Katerina Tsiggene4Dimitrios Komiotis5Nikitas Georgiou6Thomas Mavromoustakos7Stella Manta8Danielle Aje9Panagiotis Michael10Barry J. Campbell11Stamatia Papoutsopoulou12Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, GreeceDepartment of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, GreeceDepartment of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, GreeceDepartment of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, GreeceDepartment of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, GreeceDepartment of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, GreeceLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceDepartment of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, GreeceThe Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, Department of Infection Biology & Microbiomes, Institute of Infection Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 3BX, UKThe Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, Department of Infection Biology & Microbiomes, Institute of Infection Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 3BX, UKThe Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, Department of Infection Biology & Microbiomes, Institute of Infection Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 3BX, UKDepartment of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, GreeceThe NF-κB family of transcription factors is a master regulator of cellular responses during inflammation, and its dysregulation has been linked to chronic inflammatory diseases, such as inflammatory bowel disease. It is therefore of vital importance to design and test new effective NF-κB inhibitors that have the potential to be utilized in clinical practice. In this study, we used a commercial transgenic HeLa cell line as an NF-κB activation reporter to test a novel quinoline molecule, Q3, as a potential inhibitor of the canonical NF-κB pathway. Q3 inhibited NF-κB-induced luciferase in concentrations as low as 5 μM and did not interfere with cell survival or induced cell death. A real-time PCR analysis revealed that Q3 could inhibit the TNF-induced transcription of the luciferase gene, as well as the <i>TNF</i> gene, a known downstream target gene. Immunocytochemistry studies revealed that Q3 moderately interferes with TNF-induced NF-κB nuclear translocation. Moreover, docking and molecular dynamics analyses confirmed that Q3 could potentially modulate transcriptional activity by inhibiting the interaction of NF-κB and DNA. Therefore, Q3 could be potentially developed for further in vivo studies as an NF-κB inhibitor.https://www.mdpi.com/2079-7737/13/11/910NF-κBinflammationquinolinetranscription |
| spellingShingle | Panagiotis Ntavaroukas Konstantinos Michail Rafaela Tsiakalidou Eleni Stampouloglou Katerina Tsiggene Dimitrios Komiotis Nikitas Georgiou Thomas Mavromoustakos Stella Manta Danielle Aje Panagiotis Michael Barry J. Campbell Stamatia Papoutsopoulou A Novel Quinoline Inhibitor of the Canonical NF-κB Transcription Factor Pathway Biology NF-κB inflammation quinoline transcription |
| title | A Novel Quinoline Inhibitor of the Canonical NF-κB Transcription Factor Pathway |
| title_full | A Novel Quinoline Inhibitor of the Canonical NF-κB Transcription Factor Pathway |
| title_fullStr | A Novel Quinoline Inhibitor of the Canonical NF-κB Transcription Factor Pathway |
| title_full_unstemmed | A Novel Quinoline Inhibitor of the Canonical NF-κB Transcription Factor Pathway |
| title_short | A Novel Quinoline Inhibitor of the Canonical NF-κB Transcription Factor Pathway |
| title_sort | novel quinoline inhibitor of the canonical nf κb transcription factor pathway |
| topic | NF-κB inflammation quinoline transcription |
| url | https://www.mdpi.com/2079-7737/13/11/910 |
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