TY  - JOUR
A1  - Scheurer, Mario Joachim Johannes
A1  - Brands, Roman Camillus
A1  - El-Mesery, Mohamed
A1  - Hartmann, Stefan
A1  - Müller-Richter, Urs Dietmar Achim
A1  - Kübler, Alexander Christian
A1  - Seher, Axel
T1  - 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
T2  - International Journal of Molecular Science
N2  - 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.
KW  - HNSCC
KW  - NFκB
KW  - inhibitor
KW  - TPCA1
KW  - apoptosis
KW  - inflammation
KW  - TNFα
KW  - FasL
Y1  - 2019
UR  - https://opus.bibliothek.uni-wuerzburg.de/opus4-wuerzburg/frontdoor/index/index/docId/20152
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-201524
SN  - 1422-0067
VL  - 20
IS  - 6
ER  -