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The Selection of NFκB Inhibitors to Block Inflammation and Induce Sensitisation to FasL-Induced Apoptosis in HNSCC Cell Lines Is Critical for Their Use as a Prospective Cancer Therapy

Inflammation is a central aspect of tumour biology and can contribute significantly to both the origination and progression of tumours. The NFκB pathway is one of the most important signal transduction pathways in inflammation and is, therefore, an excellent target for cancer therapy. In this work,...

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Autores principales: Scheurer, Mario Joachim Johannes, Brands, Roman Camillus, El-Mesery, Mohamed, Hartmann, Stefan, Müller-Richter, Urs Dietmar Achim, Kübler, Alexander Christian, Seher, Axel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471923/
https://www.ncbi.nlm.nih.gov/pubmed/30875877
http://dx.doi.org/10.3390/ijms20061306
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author Scheurer, Mario Joachim Johannes
Brands, Roman Camillus
El-Mesery, Mohamed
Hartmann, Stefan
Müller-Richter, Urs Dietmar Achim
Kübler, Alexander Christian
Seher, Axel
author_facet Scheurer, Mario Joachim Johannes
Brands, Roman Camillus
El-Mesery, Mohamed
Hartmann, Stefan
Müller-Richter, Urs Dietmar Achim
Kübler, Alexander Christian
Seher, Axel
author_sort Scheurer, Mario Joachim Johannes
collection PubMed
description Inflammation is a central aspect of tumour biology and can contribute significantly to both the origination and progression of tumours. The NFκB pathway is one of the most important signal transduction pathways in inflammation and is, therefore, an excellent target for cancer therapy. In this work, we examined the influence of four NFκB inhibitors—Cortisol, MLN4924, QNZ and TPCA1—on proliferation, inflammation and sensitisation to apoptosis mediated by the death ligand FasL in the HNSCC cell lines PCI1, PCI9, PCI13, PCI52 and SCC25 and in the human dermal keratinocyte cell line HaCaT. We found that the selection of the inhibitor is critical to ensure that cells do not respond by inducing counteracting activities in the context of cancer therapy, e.g., the extreme IL-8 induction mediated by MLN4924 or FasL resistance mediated by Cortisol. However, TPCA1 was qualified by this in vitro study as an excellent therapeutic mediator in HNSCC by four positive qualities: (1) proliferation was inhibited at low μM-range concentrations; (2) TNFα-induced IL-8 secretion was blocked; (3) HNSCC cells were sensitized to TNFα-induced cell death; and (4) FasL-mediated apoptosis was not disrupted.
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spelling pubmed-64719232019-04-26 The Selection of NFκB Inhibitors to Block Inflammation and Induce Sensitisation to FasL-Induced Apoptosis in HNSCC Cell Lines Is Critical for Their Use as a Prospective Cancer Therapy Scheurer, Mario Joachim Johannes Brands, Roman Camillus El-Mesery, Mohamed Hartmann, Stefan Müller-Richter, Urs Dietmar Achim Kübler, Alexander Christian Seher, Axel Int J Mol Sci Article Inflammation is a central aspect of tumour biology and can contribute significantly to both the origination and progression of tumours. The NFκB pathway is one of the most important signal transduction pathways in inflammation and is, therefore, an excellent target for cancer therapy. In this work, we examined the influence of four NFκB inhibitors—Cortisol, MLN4924, QNZ and TPCA1—on proliferation, inflammation and sensitisation to apoptosis mediated by the death ligand FasL in the HNSCC cell lines PCI1, PCI9, PCI13, PCI52 and SCC25 and in the human dermal keratinocyte cell line HaCaT. We found that the selection of the inhibitor is critical to ensure that cells do not respond by inducing counteracting activities in the context of cancer therapy, e.g., the extreme IL-8 induction mediated by MLN4924 or FasL resistance mediated by Cortisol. However, TPCA1 was qualified by this in vitro study as an excellent therapeutic mediator in HNSCC by four positive qualities: (1) proliferation was inhibited at low μM-range concentrations; (2) TNFα-induced IL-8 secretion was blocked; (3) HNSCC cells were sensitized to TNFα-induced cell death; and (4) FasL-mediated apoptosis was not disrupted. MDPI 2019-03-15 /pmc/articles/PMC6471923/ /pubmed/30875877 http://dx.doi.org/10.3390/ijms20061306 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Scheurer, Mario Joachim Johannes
Brands, Roman Camillus
El-Mesery, Mohamed
Hartmann, Stefan
Müller-Richter, Urs Dietmar Achim
Kübler, Alexander Christian
Seher, Axel
The Selection of NFκB Inhibitors to Block Inflammation and Induce Sensitisation to FasL-Induced Apoptosis in HNSCC Cell Lines Is Critical for Their Use as a Prospective Cancer Therapy
title The Selection of NFκB Inhibitors to Block Inflammation and Induce Sensitisation to FasL-Induced Apoptosis in HNSCC Cell Lines Is Critical for Their Use as a Prospective Cancer Therapy
title_full The Selection of NFκB Inhibitors to Block Inflammation and Induce Sensitisation to FasL-Induced Apoptosis in HNSCC Cell Lines Is Critical for Their Use as a Prospective Cancer Therapy
title_fullStr The Selection of NFκB Inhibitors to Block Inflammation and Induce Sensitisation to FasL-Induced Apoptosis in HNSCC Cell Lines Is Critical for Their Use as a Prospective Cancer Therapy
title_full_unstemmed The Selection of NFκB Inhibitors to Block Inflammation and Induce Sensitisation to FasL-Induced Apoptosis in HNSCC Cell Lines Is Critical for Their Use as a Prospective Cancer Therapy
title_short The Selection of NFκB Inhibitors to Block Inflammation and Induce Sensitisation to FasL-Induced Apoptosis in HNSCC Cell Lines Is Critical for Their Use as a Prospective Cancer Therapy
title_sort selection of nfκb inhibitors to block inflammation and induce sensitisation to fasl-induced apoptosis in hnscc cell lines is critical for their use as a prospective cancer therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471923/
https://www.ncbi.nlm.nih.gov/pubmed/30875877
http://dx.doi.org/10.3390/ijms20061306
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