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Int. J. Mol. Sci. 2019, 20(6), 1306; https://doi.org/10.3390/ijms20061306

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

1
Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, Germany
2
Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, D-97080 Würzburg, Germany
3
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura E-35516, Egypt
4
Interdisciplinary Center for Clinical Research, University Hospital Würzburg, D-97070 Würzburg, Germany
*
Author to whom correspondence should be addressed.
Theses authors contributed equal to this work.
Received: 25 February 2019 / Revised: 11 March 2019 / Accepted: 11 March 2019 / Published: 15 March 2019
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Abstract

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. View Full-Text
Keywords: HNSCC; NFκB; inhibitor; TPCA1; apoptosis; inflammation; TNFα; FasL HNSCC; NFκB; inhibitor; TPCA1; apoptosis; inflammation; TNFα; FasL
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Scheurer, M.J.J.; Brands, R.C.; El-Mesery, M.; Hartmann, S.; Müller-Richter, U.D.A.; Kübler, A.C.; Seher, A. 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. Int. J. Mol. Sci. 2019, 20, 1306.

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