title: Metabolism of selenite in human lung cancer cells: X-ray absorption and fluorescence studies.
abstract: Selenite is an inorganic form of selenium that has a cytotoxic effect against several human cancer cell lines: one or more selenite metabolites are considered to be responsible for its toxicity. X-ray absorption spectroscopy was used to monitor Se speciation in A549 human lung cancer cells incubated with selenite over 72 h. As anticipated, selenodiglutathione and elemental Se both comprised a large proportion of Se in the cells between 4 and 72 h after treatment, which is in accordance with the reductive metabolism of selenite in the presence of glutathione and glutathione reductase/NADPH system. Selenocystine was also present in the cells but was only detected as a significant component between 24 and 48 h concomitant with a decrease in the proportion of selenocysteine and the viability of the cells. The change in speciation from the selenol, selenocysteine, to the diselenide, selenocystine, is indicative of a change in the redox status of the cells to a more oxidizing environment, likely brought about by metabolites of selenite. X-ray fluorescence microscopy of single cells treated with selenite for 24 h revealed a punctate distribution of Se in the cytoplasm. The accumulation of Se was associated with a greater than 2-fold increase in Cu, which was colocalized with Se. Selenium K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy revealed Se-Se and Se-S bonding, but not Se-Cu bonding, despite the spatial association of Se and Cu. Microprobe X-ray absorption near-edge structure spectroscopy (μ-XANES) showed that the highly localized Se species was mostly elemental Se.
authors.affiliation: School of Chemistry and Physics, The University of Adelaide, SA 5005, Australia.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Weekley
authors.forename: Jade B
authors.initials: JB
authors.lastname: Aitken
authors.forename: Stefan
authors.initials: S
authors.lastname: Vogt
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Finney
authors.forename: David J
authors.initials: DJ
authors.lastname: Paterson
authors.forename: Martin D
authors.initials: MD
authors.lastname: de Jonge
authors.forename: Daryl L
authors.initials: DL
authors.lastname: Howard
authors.forename: Paul K
authors.initials: PK
authors.lastname: Witting
authors.forename: Ian F
authors.initials: IF
authors.lastname: Musgrave
authors.forename: Hugh H
authors.initials: HH
authors.lastname: Harris
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D018038:Sodium Selenite / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D056928:X-Ray Absorption Spectroscopy
chemical_list: D000970:Antineoplastic Agents; D018038:Sodium Selenite