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Volasertib Enhances Sensitivity to TRAIL in Renal Carcinoma Caki Cells through Downregulation of c-FLIP Expression

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Author(s)
Mi-Yeon JeonKyoung-jin MinSeon Min WooSeung Un SeoShin KimJong-Wook ParkTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg KyuKim, ShinPark, Jong Wook
Department
Dept. of Immunology (면역학)
Journal Title
International Journal of Molecular Science
Issued Date
2017
Volume
18
Issue
12
Keyword
volasertibTRAILc-FLIPcaspaseapoptosis
Abstract
Polo-like kinase 1 (PLK1) plays major roles in cell cycle control and DNA damage response. Therefore, PLK1 has been investigated as a target for cancer therapy. Volasertib is the second-in class dihydropteridinone derivate that is a specific PLK1 inhibitor. In this study, we examined that combining PLK1 inhibitor with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) would have an additive and synergistic effect on induction of apoptosis in cancer cells. We found that volasertib alone and TRAIL alone had no effect on apoptosis, but the combined treatment of volasertib and TRAIL markedly induced apoptosis in Caki (renal carcinoma), A498 (renal carcinoma) and A549 (lung carcinoma) cells, but not in normal cells (human skin fibroblast cells and mesangial cells). Combined treatment induced accumulation of sub-G1 phase, DNA fragmentation, cleavage of poly (ADP-ribose) polymerase (PARP) and activation of caspase 3 activity in Caki cells. Interestingly, combined treatment induced downregulation of cellular-FLICE-inhibitory protein (c-FLIP) expression and ectopic expression of c-FLIP markedly blocked combined treatment-induced apoptosis. Therefore, this study demonstrates that volasertib may sensitize TRAIL-induced apoptosis in Caki cells via downregulation of c-FLIP. View Full-Text
Keimyung Author(s)(Kor)
권택규
김신
박종욱
Publisher
School of Medicine (의과대학)
Citation
Mi-Yeon Jeon et al. (2017). Volasertib Enhances Sensitivity to TRAIL in Renal Carcinoma Caki Cells through Downregulation of c-FLIP Expression. International Journal of Molecular Science, 18(12), 2568–2568. doi: 10.3390/ijms18122568
Type
Article
ISSN
422-0067
DOI
10.3390/ijms18122568
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/41580
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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