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Int. J. Mol. Sci. 2017, 18(12), 2568; https://doi.org/10.3390/ijms18122568

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

Department of Immunology, School of Mediine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Korea
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Received: 2 November 2017 / Revised: 28 November 2017 / Accepted: 28 November 2017 / Published: 29 November 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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
Keywords: volasertib; TRAIL; c-FLIP; caspase; apoptosis volasertib; TRAIL; c-FLIP; caspase; apoptosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Jeon, M.-Y.; Min, K.-J.; Woo, S.M.; Seo, S.U.; Kim, S.; Park, J.-W.; Kwon, T.K. Volasertib Enhances Sensitivity to TRAIL in Renal Carcinoma Caki Cells through Downregulation of c-FLIP Expression. Int. J. Mol. Sci. 2017, 18, 2568.

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