{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Takchi R"],"funding":["U.S. Department of Defense","NCI NIH HHS","U.S. Department of Health & Human Services | National Institutes of Health"],"pagination":["309"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11066049"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(5)"],"pubmed_abstract":["Sigma-2-ligands (S2L) are characterized by high binding affinities to their cognate sigma-2 receptor, overexpressed in rapidly proliferating tumor cells. As such, S2L were developed as imaging probes (ISO1) or as cancer therapeutics, alone (SV119 [C6], SW43 [C10]) and as delivery vehicles for cytotoxic drug cargoes (C6-Erastin, C10-SMAC). However, the exact mechanism of S2L-induced cytotoxicity remains to be fully elucidated. A series of high-affinity S2L were evaluated regarding their cytotoxicity profiles across cancer cell lines. While C6 and C10 displayed distinct cytotoxicities, C0 and ISO1 were essentially non-toxic. Confocal microscopy and lipidomics analysis in cellular and mouse models revealed that C10 induced increases in intralysosomal free cholesterol and in cholesterol esters"],"journal":["Cell death & disease"],"pubmed_title":["Cytotoxic sigma-2 ligands trigger cancer cell death via cholesterol-induced-ER-stress."],"pmcid":["PMC11066049"],"funding_grant_id":["R01 CA276378","R01 CA163764","W81XWH-17-1-0102"],"pubmed_authors":["Takchi R","Hawkins WG","Gong Q","Prudner BC","Spitzer D","Hagi T","Van Tine BA","Jin LX","Newcomer KF","Vangveravong S"],"additional_accession":[]},"is_claimable":false,"name":"Cytotoxic sigma-2 ligands trigger cancer cell death via cholesterol-induced-ER-stress.","description":"Sigma-2-ligands (S2L) are characterized by high binding affinities to their cognate sigma-2 receptor, overexpressed in rapidly proliferating tumor cells. As such, S2L were developed as imaging probes (ISO1) or as cancer therapeutics, alone (SV119 [C6], SW43 [C10]) and as delivery vehicles for cytotoxic drug cargoes (C6-Erastin, C10-SMAC). However, the exact mechanism of S2L-induced cytotoxicity remains to be fully elucidated. A series of high-affinity S2L were evaluated regarding their cytotoxicity profiles across cancer cell lines. While C6 and C10 displayed distinct cytotoxicities, C0 and ISO1 were essentially non-toxic. Confocal microscopy and lipidomics analysis in cellular and mouse models revealed that C10 induced increases in intralysosomal free cholesterol and in cholesterol esters","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-03T03:53:10.968Z","creation":"2026-04-24T03:09:08.928Z"},"accession":"S-EPMC11066049","cross_references":{"pubmed":["38697978"],"doi":["10.1038/s41419-024-06693-8"]}}