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Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells

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Author(s)
Kyoung-jin MinTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Cancers (Basel)
Issued Date
2020
Volume
12
Issue
11
Keyword
FTY720non-apoptotic cell deathLMPcathepsinsglioma
Abstract
FTY720, a sphingosine-1-phosphate (S1P) receptor modulator, is a synthetic compound produced by the modification of a metabolite from I. sinclairii. Here, we found that FTY720 induced non-apoptotic cell death in human glioma cells (U251MG, U87MG, and U118MG). FTY720 (10 µM) dramatically induced cytoplasmic vacuolation in glioma cells. However, FTY720-mediated vacuolation and cell death are not associated with autophagy. Genetic or pharmacological inhibition of autophagy did not inhibit FTY720-induced cell death. Herein, we detected that FTY720-induced cytoplasmic vacuoles were stained with lysotracker red, and FTY720 induced lysosomal membrane permeabilization (LMP). Interestingly, cathepsin inhibitors (E64D and pepstatin A) and ectopic expression of heat shock protein 70 (HSP70), which is an endogenous inhibitor of LMP, markedly inhibited FTY720-induced cell death. Our results demonstrated that FTY720 induced non-apoptotic cell death via the induction of LMP in human glioma cells.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Citation
Kyoung-jin Min and Taeg Kyu Kwon. (2020). Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells. Cancers (Basel), 12(11), 3388. doi: 10.3390/cancers12113388
Type
Article
ISSN
2072-6694
Source
https://www.mdpi.com/2072-6694/12/11/3388
DOI
10.3390/cancers12113388
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43433
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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