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. sinclairii. Here, we found that FTY720 induced non-apoptotic cell death in human glioma cells (U251MG, U87MG, and U118MG). FTY720 (10 µM) dramatically induced cyto...
Gespeichert in:
| Veröffentlicht in: | Cancers 2020-11, Vol.12 (11), p.3388 |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 11 |
| container_start_page | 3388 |
| container_title | Cancers |
| container_volume | 12 |
| creator | Min, Kyoung-jin Kwon, Taeg Kyu |
| description | 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. |
| doi_str_mv | 10.3390/cancers12113388 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7696845</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A645023767</galeid><sourcerecordid>A645023767</sourcerecordid><originalsourceid>FETCH-LOGICAL-c492t-d1cdce7443d42a39ba74cd745371ad35694b2bd111a3521f4af97b6c90af831d3</originalsourceid><addsrcrecordid>eNpdkktvGyEUhVHVqoncrLtF6qabaXgZzKaS5eZhyW67SBddoTvAJFgz4MJMpHTbP17sRH2EDUjn45x74SL0lpIPnGtybiFanwtllHK-WLxAp4wo1kipxct_ziforJQdqYtzqqR6jU44r6pk-hT9Wkc32TGkiFOHNw8llTRAj7d-aDNEj7_6PHhoQx9-whFbFwx4C7uU8cW9j-Ph3uXNd8VIs_UuwOgd_pxis9yn_ZjGYPHK9z3-5GG8wyHi62mAiK_6UHOOUnmDXnXQF3_2tM_Qt8uLm9V1s_lytV4tN40Vmo2No9ZZr4TgTjDgugUlrFNizhUFx-e11Za1jlIKfM5oJ6DTqpVWE-gWnDo-Qx8fffdTO_jqFccMvdnnMEB-MAmC-V-J4c7cpnujpJaLmjND758Mcvox-TKaIRRbW6gPlaZimJBMEC0Fqei7Z-guTTnW9o6U1Fwx9pe6hd6bELtUc-3B1CylmBPG639V6vyRsjmVkn33p2RKzGESzLNJ4L8BU8yldQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2462693722</pqid></control><display><type>article</type><title>Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Min, Kyoung-jin ; Kwon, Taeg Kyu</creator><creatorcontrib>Min, Kyoung-jin ; Kwon, Taeg Kyu</creatorcontrib><description>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.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers12113388</identifier><identifier>PMID: 33207629</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Apoptosis ; Autophagy ; Cancer ; Cell death ; Ectopic expression ; FTY720 ; Glioma cells ; Gliomas ; Health aspects ; Heat shock proteins ; Hsp70 protein ; Kinases ; Metabolites ; Phagocytosis ; Physiological aspects ; Sphingosine 1-phosphate ; Vacuoles</subject><ispartof>Cancers, 2020-11, Vol.12 (11), p.3388</ispartof><rights>COPYRIGHT 2020 MDPI AG</rights><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-d1cdce7443d42a39ba74cd745371ad35694b2bd111a3521f4af97b6c90af831d3</citedby><cites>FETCH-LOGICAL-c492t-d1cdce7443d42a39ba74cd745371ad35694b2bd111a3521f4af97b6c90af831d3</cites><orcidid>0000-0003-1204-2059</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696845/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696845/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids></links><search><creatorcontrib>Min, Kyoung-jin</creatorcontrib><creatorcontrib>Kwon, Taeg Kyu</creatorcontrib><title>Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells</title><title>Cancers</title><description>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.</description><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Cancer</subject><subject>Cell death</subject><subject>Ectopic expression</subject><subject>FTY720</subject><subject>Glioma cells</subject><subject>Gliomas</subject><subject>Health aspects</subject><subject>Heat shock proteins</subject><subject>Hsp70 protein</subject><subject>Kinases</subject><subject>Metabolites</subject><subject>Phagocytosis</subject><subject>Physiological aspects</subject><subject>Sphingosine 1-phosphate</subject><subject>Vacuoles</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkktvGyEUhVHVqoncrLtF6qabaXgZzKaS5eZhyW67SBddoTvAJFgz4MJMpHTbP17sRH2EDUjn45x74SL0lpIPnGtybiFanwtllHK-WLxAp4wo1kipxct_ziforJQdqYtzqqR6jU44r6pk-hT9Wkc32TGkiFOHNw8llTRAj7d-aDNEj7_6PHhoQx9-whFbFwx4C7uU8cW9j-Ph3uXNd8VIs_UuwOgd_pxis9yn_ZjGYPHK9z3-5GG8wyHi62mAiK_6UHOOUnmDXnXQF3_2tM_Qt8uLm9V1s_lytV4tN40Vmo2No9ZZr4TgTjDgugUlrFNizhUFx-e11Za1jlIKfM5oJ6DTqpVWE-gWnDo-Qx8fffdTO_jqFccMvdnnMEB-MAmC-V-J4c7cpnujpJaLmjND758Mcvox-TKaIRRbW6gPlaZimJBMEC0Fqei7Z-guTTnW9o6U1Fwx9pe6hd6bELtUc-3B1CylmBPG639V6vyRsjmVkn33p2RKzGESzLNJ4L8BU8yldQ</recordid><startdate>20201116</startdate><enddate>20201116</enddate><creator>Min, Kyoung-jin</creator><creator>Kwon, Taeg Kyu</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1204-2059</orcidid></search><sort><creationdate>20201116</creationdate><title>Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells</title><author>Min, Kyoung-jin ; Kwon, Taeg Kyu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-d1cdce7443d42a39ba74cd745371ad35694b2bd111a3521f4af97b6c90af831d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Cancer</topic><topic>Cell death</topic><topic>Ectopic expression</topic><topic>FTY720</topic><topic>Glioma cells</topic><topic>Gliomas</topic><topic>Health aspects</topic><topic>Heat shock proteins</topic><topic>Hsp70 protein</topic><topic>Kinases</topic><topic>Metabolites</topic><topic>Phagocytosis</topic><topic>Physiological aspects</topic><topic>Sphingosine 1-phosphate</topic><topic>Vacuoles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Min, Kyoung-jin</creatorcontrib><creatorcontrib>Kwon, Taeg Kyu</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Min, Kyoung-jin</au><au>Kwon, Taeg Kyu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells</atitle><jtitle>Cancers</jtitle><date>2020-11-16</date><risdate>2020</risdate><volume>12</volume><issue>11</issue><spage>3388</spage><pages>3388-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><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.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>33207629</pmid><doi>10.3390/cancers12113388</doi><orcidid>https://orcid.org/0000-0003-1204-2059</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2020-11, Vol.12 (11), p.3388 |
| issn | 2072-6694 2072-6694 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7696845 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Apoptosis Autophagy Cancer Cell death Ectopic expression FTY720 Glioma cells Gliomas Health aspects Heat shock proteins Hsp70 protein Kinases Metabolites Phagocytosis Physiological aspects Sphingosine 1-phosphate Vacuoles |
| title | Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T17%3A18%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Induction%20of%20Lysosomal%20Membrane%20Permeabilization%20Is%20a%20Major%20Event%20of%20FTY720-Mediated%20Non-Apoptotic%20Cell%20Death%20in%20Human%20Glioma%20Cells&rft.jtitle=Cancers&rft.au=Min,%20Kyoung-jin&rft.date=2020-11-16&rft.volume=12&rft.issue=11&rft.spage=3388&rft.pages=3388-&rft.issn=2072-6694&rft.eissn=2072-6694&rft_id=info:doi/10.3390/cancers12113388&rft_dat=%3Cgale_pubme%3EA645023767%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2462693722&rft_id=info:pmid/33207629&rft_galeid=A645023767&rfr_iscdi=true |