{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:11:19Z","timestamp":1792113079972,"version":"4.4.0"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2013,6,10]],"date-time":"2013-06-10T00:00:00Z","timestamp":1370822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>We have previously shown that treatment of androgen-sensitive LNCaP cells with the sphingosine kinase (SK) inhibitor SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole) induces the proteasomal degradation of two N-terminal variants of SK1 (SK1a and SK1b), increases C22:0-ceramide and diadenosine 5\u2032,5\u2032\u2032\u2032-P1,P3-triphosphate (Ap3A) and reduces S1P levels, and promotes apoptosis. We have now investigated the effects of three SK inhibitors (SKi, (S)-FTY720 vinylphosphonate, and (R)-FTY720 methyl ether) on metabolite and sphingolipid levels in androgen-sensitive LNCaP and androgen-independent LNCaP-AI prostate cancer cells. The 51 kDa N-terminal variant of SK1 (SK1b) evades the proteasome in LNCaP-AI cells, and these cells do not exhibit an increase in C22:0-ceramide or Ap3A levels and do not undergo apoptosis in response to SKi. In contrast, the SK inhibitor (S)-FTY720 vinylphosphonate induces degradation of SK1b in LNCaP-AI, but not in LNCaP cells. In LNCaP-AI cells, (S)-FTY720 vinylphosphonate induces a small increase in C16:0-ceramide levels and cleavage of polyADPribose polymerase (indicative of apoptosis). Surprisingly, the level of S1P is increased by 7.8- and 12.8-fold in LNCaP and LNCaP-AI cells, respectively, on treatment with (S)-FTY720 vinylphosphonate. Finally, treatment of androgen-sensitive LNCaP cells with the SK2-selective inhibitor (R)-FTY720 methyl ether increases lysophosphatidylinositol levels, suggesting that SK2 may regulate lyso-PI metabolism in prostate cancer cells.<\/jats:p>","DOI":"10.3390\/biom3020316","type":"journal-article","created":{"date-parts":[[2013,6,10]],"date-time":"2013-06-10T11:17:56Z","timestamp":1370863076000},"page":"316-333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Roles of Sphingosine Kinase 1 and 2 in Regulating the Metabolome and Survival of Prostate Cancer Cells"],"prefix":"10.3390","volume":"3","author":[{"given":"Francesca","family":"Tonelli","sequence":"first","affiliation":[{"name":"Cell Biology Group and Pharmaceutical Analysis and Metabolomics Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal","family":"Alossaimi","sequence":"additional","affiliation":[{"name":"Cell Biology Group and Pharmaceutical Analysis and Metabolomics Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5132-8212","authenticated-orcid":false,"given":"Viswanathan","family":"Natarajan","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago Department of Pharmacology, 909 S. Wolcott Ave., Chicago, IL 60612, USA"},{"name":"University of Illinois at Chicago, Department of Medicine, 909 S. Wolcott Ave., Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Gorshkova","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago, Department of Medicine, 909 S. Wolcott Ave., Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny","family":"Berdyshev","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago, Department of Medicine, 909 S. Wolcott Ave., Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Bittman","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Queens College of the City University of New York, Flushing, New York 11367-1597, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1094-7604","authenticated-orcid":false,"given":"David","family":"Watson","sequence":"additional","affiliation":[{"name":"Cell Biology Group and Pharmaceutical Analysis and Metabolomics Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Pyne","sequence":"additional","affiliation":[{"name":"Cell Biology Group and Pharmaceutical Analysis and Metabolomics Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Pyne","sequence":"additional","affiliation":[{"name":"Cell Biology Group and Pharmaceutical Analysis and Metabolomics Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrc2875","article-title":"Sphingosine 1-phosphate and cancer","volume":"10","author":"Pyne","year":"2010","journal-title":"Nat. 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