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
JF  - 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
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201524
SN  - 1422-0067
VL  - 20
IS  - 6
ER  - 
TY  - JOUR
A1  - Wünsch, Anna Chiara
A1  - Ries, Elena
A1  - Heinzelmann, Sina
A1  - Frabschka, Andrea
A1  - Wagner, Peter Christoph
A1  - Rauch, Theresa
A1  - Koderer, Corinna
A1  - El-Mesery, Mohamed
A1  - Volland, Julian Manuel
A1  - Kübler, Alexander Christian
A1  - Hartmann, Stefan
A1  - Seher, Axel
T1  - Metabolic silencing via methionine-based amino acid restriction in head and neck cancer
JF  - Current Issues in Molecular Biology
N2  - In recent years, various forms of caloric restriction (CR) and amino acid or protein restriction (AAR or PR) have shown not only success in preventing age-associated diseases, such as type II diabetes and cardiovascular diseases, but also potential for cancer therapy. These strategies not only reprogram metabolism to low-energy metabolism (LEM), which is disadvantageous for neoplastic cells, but also significantly inhibit proliferation. Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumour types, with over 600,000 new cases diagnosed annually worldwide. With a 5-year survival rate of approximately 55%, the poor prognosis has not improved despite extensive research and new adjuvant therapies. Therefore, for the first time, we analysed the potential of methionine restriction (MetR) in selected HNSCC cell lines. We investigated the influence of MetR on cell proliferation and vitality, the compensation for MetR by homocysteine, the gene regulation of different amino acid transporters, and the influence of cisplatin on cell proliferation in different HNSCC cell lines.
KW  - amino acid restriction
KW  - caloric restriction
KW  - methionine
KW  - HNSCC
KW  - SCCHN
KW  - cisplatin
KW  - amino acid transporter
KW  - SLC-family
KW  - cell vitality
KW  - low energy metabolism
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319257
SN  - 1467-3045
VL  - 45
IS  - 6
SP  - 4557
EP  - 4573
ER  -