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Due to defects in their lysosomal hydrolysis, they accumulate at high levels and cause cytotoxicity in patients with Krabbe and Gaucher diseases, respectively. Here, we show that GalSph and GlcSph induce lysosomal membrane permeabilization, a hallmark of lysosome-dependent cell death, in human breast cancer cells (MCF7) and primary fibroblasts. Supporting lysosomal leakage as a causative event in lysosphingolipid-induced cytotoxicity, treatment of MCF7 cells with lysosome-stabilizing cholesterol prevented GalSph- and GlcSph-induced cell death almost completely. In line with this, fibroblasts from a patient with Niemann-Pick type C disease, which is caused by defective lysosomal cholesterol efflux, were significantly less sensitive to lysosphingolipid-induced lysosomal leakage and cell death. Prompted by the data showing that MCF7 cells with acquired resistance to lysosome-destabilizing cationic amphiphilic drugs (CADs) were partially resistant to the cell death induced by GalSph and GlcSph, we compared these cell death pathways with each other. Like CADs, GalSph and GlcSph activated the cyclic AMP (cAMP) signalling pathway, and cAMP-inducing forskolin sensitized cells to cell death induced by low concentrations of lysosphingolipids. Contrary to CADs, lysosphingolipid-induced cell death was independent of lysosomal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    efflux through P2X purinerigic receptor 4. These data reveal GalSph and GlcSph as lysosome-destabilizing lipids, whose putative use in cancer therapy should be further investigated. Furthermore, the data supports the development of lysosome stabilizing drugs for the treatment of Krabbe and Gaucher diseases and possibly other sphingolipidoses.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0277058","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T13:45:30Z","timestamp":1669038330000},"page":"e0277058","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Galactosyl- and glucosylsphingosine induce lysosomal membrane permeabilization and cell death in cancer cells"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0394-0538","authenticated-orcid":true,"given":"Kamilla","family":"Stahl-Meyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mesut","family":"Bilgin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lya K. K.","family":"Holland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Stahl-Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kirkegaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaj Havns\u00f8e Torp","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5950-7111","authenticated-orcid":true,"given":"Marja","family":"J\u00e4\u00e4ttel\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"issue":"3","key":"pone.0277058.ref001","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/0006-291X(72)90381-6","article-title":"Globoid cell leukodystrophy: Additional deficiency of psychosine galactosidase","volume":"48","author":"T Miyatake","year":"1972","journal-title":"Biochemical and Biophysical Research Communications"},{"issue":"3","key":"pone.0277058.ref002","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1093\/oxfordjournals.jbchem.a124584","article-title":"The synthetic pathway for glucosylsphingosine in cultured fibroblasts","volume":"116","author":"Y Yamaguchi","year":"1994","journal-title":"J Biochem"},{"issue":"7","key":"pone.0277058.ref003","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1023\/A:1020259630034","article-title":"Cationic Glycosphingolipids in Neuronal Tissues and Their Possible Biological Significance","volume":"27","author":"T Hikita","year":"2002","journal-title":"Neurochemical research"},{"issue":"3","key":"pone.0277058.ref004","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1023\/A:1022436928925","article-title":"Twenty Five Years of the \u201cPsychosine Hypothesis\u201d: A Personal Perspective of its History and Present Status","volume":"23","author":"K. Suzuki","year":"1998","journal-title":"Neurochemical research"},{"issue":"2","key":"pone.0277058.ref005","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrd.2017.214","article-title":"Emptying the stores: lysosomal diseases and therapeutic strategies","volume":"17","author":"FM Platt","year":"2018","journal-title":"Nature reviews Drug discovery"},{"issue":"2","key":"pone.0277058.ref006","doi-asserted-by":"crossref","first-page":"73","DOI":"10.15252\/emmm.201505966","article-title":"The awesome lysosome","volume":"8","author":"A. Ballabio","year":"2016","journal-title":"EMBO molecular medicine"},{"issue":"11","key":"pone.0277058.ref007","doi-asserted-by":"crossref","first-page":"e79732","DOI":"10.1371\/journal.pone.0079732","article-title":"Glucosylsphingosine is a highly sensitive and specific biomarker for primary diagnostic and follow-up monitoring in Gaucher disease in a non-Jewish, Caucasian cohort of Gaucher disease patients","volume":"8","author":"A Rolfs","year":"2013","journal-title":"PLOS One"},{"issue":"2","key":"pone.0277058.ref008","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1073\/pnas.66.2.302","article-title":"Globoid cell leucodystrophy (Krabbe\u2019s disease): deficiency of galactocerebroside beta-galactosidase","volume":"66","author":"K Suzuki","year":"1970","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pone.0277058.ref009","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/ana.410240407","article-title":"Infantile and fetal globoid cell leukodystrophy: Analysis of galactosylceramide and galactosylsphingosine","volume":"24","author":"T Kobayashi","year":"1988","journal-title":"Annals of neurology"},{"key":"pone.0277058.ref010","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0022-2275(20)39839-4","article-title":"Krabbe disease: A galactosylsphingosine (Psychosine) lipidosis","volume":"21","author":"L Svennerholm","year":"1980","journal-title":"Journal of lipid research"},{"issue":"13","key":"pone.0277058.ref011","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.cub.2005.05.057","article-title":"The Vacuolar H+-ATPase Mediates Intracellular Acidification Required for Neurodegeneration in C. elegans","volume":"15","author":"P Syntichaki","year":"2005","journal-title":"Current biology"},{"issue":"37","key":"pone.0277058.ref012","doi-asserted-by":"crossref","first-page":"12535","DOI":"10.1523\/JNEUROSCI.1920-10.2010","article-title":"Pathogenic Lysosomal Depletion in Parkinson\u2019s Disease","volume":"30","author":"B Dehay","year":"2010","journal-title":"The Journal of Neuroscience"},{"issue":"10","key":"pone.0277058.ref013","doi-asserted-by":"crossref","first-page":"4445","DOI":"10.1172\/JCI76246","article-title":"Proteinase 3-dependent caspase-3 cleavage modulates neutrophil death and inflammation","volume":"124","author":"F Loison","year":"2014","journal-title":"J Clin Invest"},{"issue":"9","key":"pone.0277058.ref014","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1242\/jcs.091181","article-title":"Lysosomal cell death at a glance","volume":"126","author":"S Aits","year":"2013","journal-title":"Journal of Cell Science"},{"issue":"3","key":"pone.0277058.ref015","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018","volume":"25","author":"L Galluzzi","year":"2018","journal-title":"Cell Death & Differentiation"},{"issue":"12","key":"pone.0277058.ref016","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1111\/tra.12613","article-title":"Lysosomal membrane permeabilization and cell death","volume":"19","author":"F Wang","year":"2018","journal-title":"Traffic"},{"issue":"1","key":"pone.0277058.ref017","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1073\/pnas.0408592102","article-title":"Induction of lysosomal membrane permeabilization by compounds that activate p53-independent apoptosis","volume":"102","author":"H Erdal","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"21","key":"pone.0277058.ref018","doi-asserted-by":"crossref","first-page":"7880","DOI":"10.1128\/MCB.00716-06","article-title":"Apoptosome-independent activation of the lysosomal cell death pathway by caspase-9","volume":"26","author":"M Gyrd-Hansen","year":"2006","journal-title":"Molecular and cellular biology"},{"issue":"9","key":"pone.0277058.ref019","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1021\/jm00195a026","article-title":"Lysosomotropic agents. 1. 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Bilgin","year":"2017","journal-title":"Methods in molecular biology (Clifton, NJ)."},{"issue":"9","key":"pone.0277058.ref037","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s11306-020-01710-1","article-title":"Cationic amphiphilic drugs induce elevation in lysoglycerophospholipid levels and cell death in leukemia cells","volume":"16","author":"I\u00d8 Nielsen","year":"2020","journal-title":"Metabolomics"},{"issue":"8","key":"pone.0277058.ref038","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/o59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"EG Bligh","year":"1959","journal-title":"Can J Biochem Physiol"},{"issue":"5","key":"pone.0277058.ref039","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/emboj.2009.6","article-title":"Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR signalling","volume":"28","author":"T Zech","year":"2009","journal-title":"The EMBO 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