Targeting inhibitors of apoptosis in oral squamous cell carcinoma in vitro

Publication date: Available online 19 July 2019Source: Journal of Cranio-Maxillofacial SurgeryAuthor(s): Mario J.J. Scheurer, Axel Seher, Valentin Steinacker, Christian Linz, Stefan Hartmann, Alexander C. Kübler, Urs D.A. Müller-Richter, Roman C. BrandsAbstractHead and neck cancer, which predominantly arises from the oral mucosa, represents the sixth most common malignancy worldwide. These cancer cells can be resistant to programmed cell death triggered by extrinsic stimuli due to innate overexpression of inhibitor of apoptosis proteins (IAPs). The cellular protein second mitochondria-derived activator of caspases (SMAC) can antagonize IAP-induced caspase inhibition and thus trigger apoptosis. Here, we investigate the cell death-sensitizing effects of the SMAC mimetic LCL161 alone and in combination with Fas ligand (FasL) using a panel of six cell lines. Fas receptor (FasR) expression was analyzed by flow cytometry. Cells were treated with FasL and LCL161 alone or in combination, and cytotoxicity was measured using crystal violet assays. Annexin V and cell viability assays using zVAD-fmk and Necrostatin-1 (Nec-1) were carried out to assess the type of programmed cell death induced by LCL161. To demonstrate the sensitizing effects of LCL161, we employed the t-test to compare the effects of FasL alone and in combination with LCL161. Linear regression analysis was performed to determine initial and half maximal inhibitory concentrations (IC10 and IC50, respectively). Distinct ...
Source: Journal of Cranio Maxillofacial Surgery - Category: ENT & OMF Source Type: research