A Novel Quinoline Inhibitor of the Canonical NF-κB Transcription Factor Pathway
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
Affiliations
Panagiotis Ntavaroukas
Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, Greece
Konstantinos Michail
Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, Greece
Rafaela Tsiakalidou
Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, Greece
Eleni Stampouloglou
Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, Greece
Katerina Tsiggene
Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, Greece
Dimitrios Komiotis
Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, Greece
Nikitas Georgiou
Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece
Thomas Mavromoustakos
Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece
Stella Manta
Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, Greece
Danielle Aje
The 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, UK
Panagiotis Michael
The 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, UK
Barry J. Campbell
The 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, UK
Stamatia Papoutsopoulou
Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, 41335 Larissa, Greece
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 TNF 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.
