title: Cytotoxic effects of SMAC-mimetic compound LCL161 in head and neck cancer cell lines.
abstract: OBJECTIVE
  Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide. Unfortunately, recent drug developments in other fields of oncology have yielded no efficacy in the treatment of oral squamous cell carcinoma. As a new starting point, we investigated the impact of Fas ligand (FasL) and the SMAC-mimetic compound LCL161 in mono- and combination treatment in HNSCC cell lines.
  
  
  METHODS
  Five different cell lines of HNSCC were treated with FasL and LCL161 in mono- and combination treatment. Cytotoxicity was measured via a crystal violet assay. The cell lines were characterized for CD95 (FasL receptor) expression via flow cytometry. The degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) was detected via Western blot.
  
  
  RESULTS
  Incubation with FasL led to a significant decrease in three out of five cell lines. Combination treatment with LCL161 enhanced cytotoxicity significantly. Two cell lines were FasL resistant, but one of them could be resensitized with LCL161. In all cell lines, Western blot analysis showed degradation of cIAP1 after LCL161 application. However, one cell line showed only minor vulnerability to the FasL and LCL161 combination.
  
  
  CONCLUSIONS
  This is the first study investigating combination treatment of FasL and LCL161 in head and neck cancer cell lines. Pro-apoptotic effects of the combination were detected in the majority of the cell lines. Interestingly, one of two FasL-resistant cell lines was sensitive to the combination therapy with FasL and LCL161.
  
  
  CONCLUSIONS
  SMAC-mimetic compounds show promising results in the treatment of other tumor entities in vitro and might be useful drugs to improve HNSCC therapy.
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany. brands_r@ukw.de.|Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Josef-Schneider-Str. 6, 97070, Würzburg, Germany. brands_r@ukw.de.
authors: Roman C
authors: RC
authors: Brands
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors: Franziska
authors: F
authors: Herbst
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.|Interdisciplinary Center for Clinical Research, University Hospital Würzburg, Josef-Schneider-Str. 2, 97070, Würzburg, Germany.
authors: Stefan
authors: S
authors: Hartmann
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors: Axel
authors: A
authors: Seher
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors: Christian
authors: C
authors: Linz
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors: Alexander C
authors: AC
authors: Kübler
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors: Urs D A
authors: UDA
authors: Müller-Richter
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004359:Drug Therapy, Combination; D053222:Fas Ligand Protein / Q000494:pharmacology*; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D019014:fas Receptor / Q000378:metabolism
chemical_list: C491901:FAS protein, human; D053222:Fas Ligand Protein; D051034:Inhibitor of Apoptosis Proteins; C574246:LCL161; D013844:Thiazoles; D019014:fas Receptor
keywords: HNSCC; LCL161; SMAC mimetic compound; Small molecules; Targeted therapy