title: Investigation of the selenium metabolism in cancer cell lines.
abstract: The aim of this work was to compare different selenium species for their ability to induce cell death in different cancer cell lines, while investigating the underlying chemistry by speciation analysis. A prostate cancer cell line (PC-3), a colon cancer cell line (HT-29) and a leukaemia cell line (Jurkat E6-1) were incubated with five selenium compounds representing inorganic as well as organic Se compounds in different oxidation states. Selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), methylseleninic acid (MeSeA), selenite and selenate in the concentration range 5-100 μM were incubated with cells for 24 h and the induction of cell death was measured using flow cytometry. The amounts of total selenium in cell medium, cell lysate and the insoluble fractions was determined by ICP-MS. Speciation analysis of cellular fractions was performed by reversed phase, anion exchange and size exclusion chromatography and ICP-MS detection. The selenium compounds exhibited large differences in their ability to induce cell death in the three cell lines and the susceptibilities of the cell lines were different. Full recovery of selenium in the cellular fractions was observed for all Se compounds except MeSeA. Speciation analysis showed that MeSeA was completely transformed during the incubations, while metabolic conversion of the other Se compounds was limited. Production of volatile dimethyl diselenide was observed for MeSeA and MeSeCys. MeSeA, MeSeCys and selenite showed noticeable protein binding. Correlations between cell death induction and the Se compounds transformations could not be demonstrated.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Lunøe
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gabel-Jensen
authors.forename: Stefan
authors.initials: S
authors.lastname: Stürup
authors.forename: Lars
authors.initials: L
authors.lastname: Andresen
authors.forename: Søren
authors.initials: S
authors.lastname: Skov
authors.forename: Bente
authors.initials: B
authors.lastname: Gammelgaard
mesh_terms: D045744:Cell Line, Tumor; D019073:HT29 Cells; D006801:Humans; D019169:Jurkat Cells; D013058:Mass Spectrometry; D009369:Neoplasms / Q000737:chemistry / Q000378:metabolism*; D016566:Organoselenium Compounds / Q000737:chemistry / Q000378:metabolism*; D012643:Selenium / Q000737:chemistry / Q000378:metabolism*; D018036:Selenium Compounds / Q000737:chemistry / Q000378:metabolism*; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism
chemical_list: D016566:Organoselenium Compounds; D018036:Selenium Compounds; D012643:Selenium