Oncotarget

Research Papers:

YM155 sensitizes TRAIL-induced apoptosis through cathepsin S-dependent down-regulation of Mcl-1 and NF-κB-mediated down-regulation of c-FLIP expression in human renal carcinoma Caki cells

Seon Min Woo, Kyoung-jin Min, Bo Ram Seo and Taeg Kyu Kwon _

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Oncotarget. 2016; 7:61520-61532. https://doi.org/10.18632/oncotarget.11137

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Abstract

Seon Min Woo1,*, Kyoung-jin Min1,*, Bo Ram Seo1, Taeg Kyu Kwon1

1Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, South Korea

*These authors have contributed equally to this work

Correspondence to:

Taeg Kyu Kwon, email: [email protected]

Keywords: YM155, TRAIL, Mcl-1, c-FLIP, lysosome, NF-κB

Received: April 4, 2016     Accepted: July 27, 2016     Published: August 9, 2016

ABSTRACT

YM155, a small-molecule survivin inhibitor, has been reported for its anti-cancer activity in various cancer cells. In this study, we investigated the effect of YM155 to enhance TRAIL-mediated apoptosis in human renal carcinoma cells. We found that YM155 alone had no effect on apoptosis, however, combined treatment with YM155 and TRAIL markedly induced apoptosis in human renal carcinoma cells (Caki, ACHN, and A498), breast cancer cells (MDA-MB231), and glioma cells (U251MG), but not normal cells [mesangial cell (MC) and human skin fibroblast (HSF)]. YM155 induced down-regulation of Mcl-1 expression at the post-translational levels, and the overexpression of Mcl-1 markedly inhibited YM155 plus TRAIL-induced apoptosis. Furthermore, YM155 induced down-regulation of c-FLIP mRNA expression through inhibition of NF-κB transcriptional activity. Ectopic expression of c-FLIP markedly blocked YM155-induced TRAIL sensitization. Taken together, our results suggested that YM155 sensitizes TRAIL-mediated apoptosis via down-regulation of Mcl-1 and c-FLIP expression in renal carcinoma Caki cells.


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