PMID- 29467909 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 15 IP - 3 DP - 2018 Mar TI - Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines. PG - 4010-4016 LID - 10.3892/ol.2018.7783 [doi] AB - 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 (IC(10)) 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 (IC(10)) 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. FAU - Brands, Roman C AU - Brands RC AD - Department of Oral and Maxillofacial Plastic Surgery, University Hospital Wurzburg, D-97070 Wurzburg, Germany. AD - Comprehensive Cancer Center Mainfranken, University Hospital Wurzburg, D-97080 Wurzburg, Germany. FAU - Scheurer, Mario J J AU - Scheurer MJJ AD - Department of Oral and Maxillofacial Plastic Surgery, University Hospital Wurzburg, D-97070 Wurzburg, Germany. FAU - Hartmann, Stefan AU - Hartmann S AD - Department of Oral and Maxillofacial Plastic Surgery, University Hospital Wurzburg, D-97070 Wurzburg, Germany. AD - Interdisciplinary Center for Clinical Research, University Hospital Wurzburg, D-97070 Wurzburg, Germany. FAU - Seher, Axel AU - Seher A AD - Department of Oral and Maxillofacial Plastic Surgery, University Hospital Wurzburg, D-97070 Wurzburg, Germany. FAU - Kubler, Alexander C AU - Kubler AC AD - Department of Oral and Maxillofacial Plastic Surgery, University Hospital Wurzburg, D-97070 Wurzburg, Germany. FAU - Muller-Richter, Urs D A AU - Muller-Richter UDA AD - Department of Oral and Maxillofacial Plastic Surgery, University Hospital Wurzburg, D-97070 Wurzburg, Germany. LA - eng PT - Journal Article DEP - 20180112 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC5796371 OTO - NOTNLM OT - apoptosis OT - head and neck squamous cell carcinoma OT - inhibitor of apoptosis OT - second mitochondria-derived activator of caspase EDAT- 2018/02/23 06:00 MHDA- 2018/02/23 06:01 PMCR- 2018/01/12 CRDT- 2018/02/23 06:00 PHST- 2017/07/24 00:00 [received] PHST- 2017/10/20 00:00 [accepted] PHST- 2018/02/23 06:00 [entrez] PHST- 2018/02/23 06:00 [pubmed] PHST- 2018/02/23 06:01 [medline] PHST- 2018/01/12 00:00 [pmc-release] AID - OL-0-0-7783 [pii] AID - 10.3892/ol.2018.7783 [doi] PST - ppublish SO - Oncol Lett. 2018 Mar;15(3):4010-4016. doi: 10.3892/ol.2018.7783. Epub 2018 Jan 12.