Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines

  • Authors:
    • Roman C. Brands
    • Mario J.J. Scheurer
    • Stefan Hartmann
    • Axel Seher
    • Alexander C. Kübler
    • Urs D.A. Müller‑Richter
  • View Affiliations

  • Published online on: January 12, 2018     https://doi.org/10.3892/ol.2018.7783
  • Pages: 4010-4016
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Abstract

Inhibitor of apoptosis proteins, which are overexpressed in head and neck squamous cell carcinoma (HNSCC), may cause therapeutic resistance. Using SMAC mimetic compounds, including birinapant, to degrade and/or inhibit these proteins and sensitize apoptosis may enhance therapies in HNSCC. Fas expression was analyzed in nine HNSCC cell lines and one keratinocyte cell line via flow cytometry. These cell lines were treated with Fas ligand‑Fc (FasL) and birinapant, a bivalent SMAC mimetic, in mono and combination therapies. Cytotoxicity was measured using a crystal violet assay. Annexin V assay was performed for detection of apoptosis. The treatment efficacy of mono and combination therapies was statistically analyzed. Nonlinear regression analysis was performed to determine the inhibitory concentration (IC10) of birinapant. Fas expression was detected in each cell line tested. Mono treatment with FasL revealed minor to no apoptotic effects in the majority of the cell lines. Crystal violet and Annexin V staining revealed increased apoptosis rates for all cell lines following incubation with birinapant in mono treatment. Combination treatment with FasL and birinapant (IC10) revealed additional and synergistic effects in eight out of the ten cell lines. To the best of our knowledge, the present study provided the first evidence of the apoptosis‑sensitizing activity of combination treatment with FasL and birinapant in HNSCC cell lines.
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March-2018
Volume 15 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Brands RC, Scheurer MJ, Hartmann S, Seher A, Kübler AC and Müller‑Richter UD: Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines. Oncol Lett 15: 4010-4016, 2018
APA
Brands, R.C., Scheurer, M.J., Hartmann, S., Seher, A., Kübler, A.C., & Müller‑Richter, U.D. (2018). Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines. Oncology Letters, 15, 4010-4016. https://doi.org/10.3892/ol.2018.7783
MLA
Brands, R. C., Scheurer, M. J., Hartmann, S., Seher, A., Kübler, A. C., Müller‑Richter, U. D."Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines". Oncology Letters 15.3 (2018): 4010-4016.
Chicago
Brands, R. C., Scheurer, M. J., Hartmann, S., Seher, A., Kübler, A. C., Müller‑Richter, U. D."Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines". Oncology Letters 15, no. 3 (2018): 4010-4016. https://doi.org/10.3892/ol.2018.7783