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Sensitization of head and neck squamous cell carcinoma to apoptosis by combinational SMAC mimetic and Fas ligand-Fc treatment in vitro

This study aimed to investigate the in vitro efficacy of three different SMAC mimetics for pro-apoptotic sensitization of HNSCC cells. We evaluated BV-6 in comparison to Birinapant and LCL161, for which pro-apoptotic sensitization effects have been demonstrated. Concentration-dependent response was...

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Main Authors: Brands, Roman C. (Author) , Scheurer, Mario J. J. (Author) , Hartmann, Stefan (Author) , Seher, Axel (Author) , Freudlsperger, Christian (Author) , Moratin, Julius (Author) , Linz, Christian (Author) , Kübler, Alexander (Author) , Müller-Richter, Urs (Author)
Format: Article (Journal)
Language:English
Published: 2 June 2020
In: Journal of cranio-maxillofacial surgery
Year: 2020, Volume: 48, Issue: 7, Pages: 685-693
ISSN:1878-4119
DOI:10.1016/j.jcms.2020.05.007
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jcms.2020.05.007
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S1010518220301281
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Author Notes:Roman C. Brands, Mario J.J. Scheurer, Stefan Hartmann, Axel Seher, Christian Freudlsperger, Julius Moratin, Christian Linz, Alexander C. Kübler, Urs D.A. Müller-Richter
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Summary:This study aimed to investigate the in vitro efficacy of three different SMAC mimetics for pro-apoptotic sensitization of HNSCC cells. We evaluated BV-6 in comparison to Birinapant and LCL161, for which pro-apoptotic sensitization effects have been demonstrated. Concentration-dependent response was measured for BV-6 in each cell line with an average IC50 value 8-fold lower than of aforementioned SMAC mimetics. Combination treatment of FasL (log2) and BV-6 (IC10) showed highly significant cell count reductions even in the lowest applied concentration in five cell lines (PCI-1: p = 0.0002, PCI-13: p = 0.0002, Detroit 562: p: p < 0.0001, FaDu: p < 0.0001, SCC-25: p = 0.0047). Synergistic effects (y < 1) were evident in eight out of 10 cell lines (PCI-1, PCI-9, PCI-13, PCI-68, Detroit 562, FaDu, SCC-25 and HaCaT). Annexin V assays revealed in nine cell lines very highly significant (p < 0.001) pro-apoptotic effects of BV-6. Western blots showed a heterogeneous IAP expression following SMAC mimetic treatment. Except for two cell lines, at least the cellular inhibitor of apoptosis protein 1 (cIAP1) was degraded in response to BV-6. For prospective targeted HNSCC therapy, this study identifies SMAC mimetics, particularly BV-6 as the compound with the highest pro-apoptotic potency, as promising antitumor agents.
Item Description:Gesehen am 13.08.2020
Physical Description:Online Resource
ISSN:1878-4119
DOI:10.1016/j.jcms.2020.05.007

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