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http://dx.doi.org/10.5352/JLS.2019.29.3.318

YM155 Induces Apoptosis through Downregulation of Anti-apoptotic Proteins in Head and Neck AMC-HN4 Cells  

Chang, Ho Joon (Department of Otolaryngology, School of Medicine, Keimyung University)
Kwon, Taeg Kyu (Department of Immunology, School of Medicine, Keimyung University)
Kim, Dong Eun (Department of Otolaryngology, School of Medicine, Keimyung University)
Publication Information
Journal of Life Science / v.29, no.3, 2019 , pp. 318-324 More about this Journal
Abstract
Squamous cell carcinoma is the primary tumor type in head and neck cancers, the fifth most common malignant neoplasm world-wide. Survivin, a member of the inhibitor of apoptosis family, is highly expressed in head and neck carcinoma patients and correlated with more aggressive forms. In this study, we investigated whether YM155, a specific survivin inhibitor, could induce apoptosis in head and neck AMC-HN4 cells. YM155 was found to markedly induce apoptosis and cleavage of PARP, a marker of apoptosis. Furthermore, YM155 promoted apoptosis in other cancer cells, such as glioma (U251MG) and renal carcinoma (Caki) cells. In contrast, YM155 had no effect on apoptosis in normal mesangial cells. YM155 significantly induced caspase activation, and pan caspase inhibitor z-VAD-fmk markedly blocked apoptosis, PARP cleavage, and caspase-3 cleavage. Therefore, YM155 was seen to instigate caspase-dependent apoptosis in head and neck AMC-HN4 cells, inducing downregulation of survivin as well as other apoptotic proteins such as c-FLIP and Mcl-1. In addition, the induction of apoptosis and PARP cleavage by YM155 treatment was effectively inhibited in survivin-, c-FLIP- and Mcl-1-over-expressing head and neck AMC-HN4 cells. In conclusion, YM155 is a potent candidate for inducing cell death in head and neck AMC-HN4 cells.
Keywords
Apoptosis; apoptotic proteins; head and neck carcinoma; survivin; YM155;
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