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

Oncology Letters
Roman C BrandsUrs D A Müller-Richter

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...Continue Reading

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May 25, 2021·Frontiers in Oncology·Yuzuka KannoYin-Ju Chen

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