Inhibition of Drp1 Sensitizes Cancer Cells to Cisplatin-Induced Apoptosis through Transcriptional Inhibition of c-FLIP Expression
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 dysfunctio...
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doaj-9c786ba10693486dab02f955a1f829952020-12-09T00:04:24ZengMDPI AGMolecules1420-30492020-12-01255793579310.3390/molecules25245793Inhibition of Drp1 Sensitizes Cancer Cells to Cisplatin-Induced Apoptosis through Transcriptional Inhibition of c-FLIP ExpressionSeon Min Woo0Kyoung-jin Min1Taeg Kyu Kwon2Department of Immunology, School of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 42601, KoreaDepartment of Immunology, School of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 42601, KoreaDepartment of Immunology, School of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 42601, KoreaMitochondrial 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 mM). 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.https://www.mdpi.com/1420-3049/25/24/5793Mdivi-1cisplatinapoptosisc-FLIPDrp1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Seon Min Woo Kyoung-jin Min Taeg Kyu Kwon |
spellingShingle |
Seon Min Woo Kyoung-jin Min Taeg Kyu Kwon Inhibition of Drp1 Sensitizes Cancer Cells to Cisplatin-Induced Apoptosis through Transcriptional Inhibition of c-FLIP Expression Molecules Mdivi-1 cisplatin apoptosis c-FLIP Drp1 |
author_facet |
Seon Min Woo Kyoung-jin Min Taeg Kyu Kwon |
author_sort |
Seon Min Woo |
title |
Inhibition of Drp1 Sensitizes Cancer Cells to Cisplatin-Induced Apoptosis through Transcriptional Inhibition of c-FLIP Expression |
title_short |
Inhibition of Drp1 Sensitizes Cancer Cells to Cisplatin-Induced Apoptosis through Transcriptional Inhibition of c-FLIP Expression |
title_full |
Inhibition of Drp1 Sensitizes Cancer Cells to Cisplatin-Induced Apoptosis through Transcriptional Inhibition of c-FLIP Expression |
title_fullStr |
Inhibition of Drp1 Sensitizes Cancer Cells to Cisplatin-Induced Apoptosis through Transcriptional Inhibition of c-FLIP Expression |
title_full_unstemmed |
Inhibition of Drp1 Sensitizes Cancer Cells to Cisplatin-Induced Apoptosis through Transcriptional Inhibition of c-FLIP Expression |
title_sort |
inhibition of drp1 sensitizes cancer cells to cisplatin-induced apoptosis through transcriptional inhibition of c-flip expression |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2020-12-01 |
description |
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 mM). 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. |
topic |
Mdivi-1 cisplatin apoptosis c-FLIP Drp1 |
url |
https://www.mdpi.com/1420-3049/25/24/5793 |
work_keys_str_mv |
AT seonminwoo inhibitionofdrp1sensitizescancercellstocisplatininducedapoptosisthroughtranscriptionalinhibitionofcflipexpression AT kyoungjinmin inhibitionofdrp1sensitizescancercellstocisplatininducedapoptosisthroughtranscriptionalinhibitionofcflipexpression AT taegkyukwon inhibitionofdrp1sensitizescancercellstocisplatininducedapoptosisthroughtranscriptionalinhibitionofcflipexpression |
_version_ |
1724388660715978752 |