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Inhibition of Drp1 Sensitizes Cancer Cells to Cisplatin-Induced Apoptosis through Transcriptional Inhibition of c-FLIP Expression

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Author(s)
Seon Min WooKyoung-jin MinTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Molecules
Issued Date
2020
Volume
25
Issue
24
Keyword
Mdivi-1cisplatinapoptosisc-FLIPDrp1
Abstract
Mitochondrial fragmentation occurs during the apoptosis. Dynamin-related protein 1 (Drp1) acts as an important component in mitochondrial fission machinery and can regulate various biological processes including apoptosis, cell cycle, and proliferation. The present study demonstrates that dysfunction of mitochondrial dynamics plays a pivotal role in cisplatin-induced apoptosis. Inhibiting the mitochondrial fission with the specific inhibitor (Mdivi-1) did not affect apoptotic cell death in low concentrations (<10 μM). Interestingly, mdivi-1 enhanced cisplatin-induced apoptosis in cancer cells, but not in normal cells. Particularly in the presence of mdivi-1, several human cancer cell lines, including renal carcinoma cell line Caki-1, became vulnerable to cisplatin by demonstrating the traits of caspase 3-dependent apoptosis. Combined treatment induced downregulation of c-FLIP expression transcriptionally, and ectopic expression of c-FLIP attenuated combined treatment-induced apoptotic cell death with mdivi-1 plus cisplatin. Collectively, our data provide evidence that mdivi-1 might be a cisplatin sensitizer.
Keimyung Author(s)(Kor)
우선민
민경진
권택규
Publisher
School of Medicine (의과대학)
Citation
Seon Min Woo et al. (2020). Inhibition of Drp1 Sensitizes Cancer Cells to Cisplatin-Induced Apoptosis through Transcriptional Inhibition of c-FLIP Expression. Molecules, 25(24), 5793. doi: 10.3390/molecules25245793
Type
Article
ISSN
1420-3049
Source
https://www.mdpi.com/1420-3049/25/24/5793
DOI
10.3390/molecules25245793
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43471
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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