Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells
FTY720, a sphingosine-1-phosphate (S1P) receptor modulator, is a synthetic compound produced by the modification of a metabolite from <i>I. sinclairii</i>. Here, we found that FTY720 induced non-apoptotic cell death in human glioma cells (U251MG, U87MG, and U118MG). FTY720 (10 µM) dramat...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/11/3388 |
| _version_ | 1797547801987514368 |
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| author | Kyoung-jin Min Taeg Kyu Kwon |
| author_facet | Kyoung-jin Min Taeg Kyu Kwon |
| author_sort | Kyoung-jin Min |
| collection | DOAJ |
| description | FTY720, a sphingosine-1-phosphate (S1P) receptor modulator, is a synthetic compound produced by the modification of a metabolite from <i>I. sinclairii</i>. 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. |
| first_indexed | 2024-03-10T14:49:24Z |
| format | Article |
| id | doaj.art-087f627c05884307af938221ef539410 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T14:49:24Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-087f627c05884307af938221ef5394102023-11-20T21:04:59ZengMDPI AGCancers2072-66942020-11-011211338810.3390/cancers12113388Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma CellsKyoung-jin Min0Taeg Kyu Kwon1Department 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, KoreaFTY720, a sphingosine-1-phosphate (S1P) receptor modulator, is a synthetic compound produced by the modification of a metabolite from <i>I. sinclairii</i>. 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.https://www.mdpi.com/2072-6694/12/11/3388FTY720non-apoptotic cell deathLMPcathepsinsglioma |
| spellingShingle | Kyoung-jin Min Taeg Kyu Kwon Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells Cancers FTY720 non-apoptotic cell death LMP cathepsins glioma |
| title | Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells |
| title_full | Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells |
| title_fullStr | Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells |
| title_full_unstemmed | Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells |
| title_short | Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells |
| title_sort | induction of lysosomal membrane permeabilization is a major event of fty720 mediated non apoptotic cell death in human glioma cells |
| topic | FTY720 non-apoptotic cell death LMP cathepsins glioma |
| url | https://www.mdpi.com/2072-6694/12/11/3388 |
| work_keys_str_mv | AT kyoungjinmin inductionoflysosomalmembranepermeabilizationisamajoreventoffty720mediatednonapoptoticcelldeathinhumangliomacells AT taegkyukwon inductionoflysosomalmembranepermeabilizationisamajoreventoffty720mediatednonapoptoticcelldeathinhumangliomacells |