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

Roman C Brands1,2, Mario J J Scheurer1, Stefan Hartmann1,3

  • 1Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, Germany.

Oncology Letters
|February 23, 2018
PubMed

Insights

This study shows that combining birinapant with Fas ligand enhances apoptosis in head and neck squamous cell carcinoma (HNSCC) cells. This combination therapy offers a promising strategy to overcome therapeutic resistance in HNSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Inhibitor of apoptosis proteins (IAPs) are overexpressed in head and neck squamous cell carcinoma (HNSCC), contributing to therapeutic resistance.
  • SMAC mimetic compounds, like birinapant, can degrade or inhibit IAPs, potentially sensitizing cancer cells to apoptosis and enhancing treatment efficacy.

Purpose of the Study:

  • To investigate the efficacy of combining birinapant with Fas ligand (FasL) in sensitizing HNSCC cell lines to apoptosis.
  • To evaluate the synergistic effects of this combination therapy on HNSCC cell cytotoxicity.

Main Methods:

  • Fas expression was analyzed in HNSCC cell lines using flow cytometry.
  • Cell lines were treated with FasL and birinapant (a bivalent SMAC mimetic) in mono and combination therapies.
  • Cytotoxicity was assessed via crystal violet assay, and apoptosis was measured using Annexin V staining.

Main Results:

  • Fas expression was detected in all tested HNSCC cell lines.
  • Birinapant monotherapy increased apoptosis rates across all cell lines.
  • Combination treatment with FasL and birinapant (at IC10) demonstrated additional and synergistic apoptotic effects in 80% of the HNSCC cell lines.

Conclusions:

  • This study provides the first evidence of apoptosis-sensitizing activity of combined FasL and birinapant treatment in HNSCC cell lines.
  • The combination of birinapant and FasL shows potential as a novel therapeutic strategy to overcome resistance in HNSCC.
Keywords:
apoptosishead and neck squamous cell carcinomainhibitor of apoptosissecond mitochondria-derived activator of caspase

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