Metabolism of selenite in human lung cancer cells: X-ray absorption and fluorescence studies
Date
2011
Authors
Weekley, C.
Aitken, J.
Vogt, S.
Finney, L.
Paterson, D.
De Jonge, M.
Howard, D.
Witting, P.
Musgrave, I.
Harris, H.
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Journal article
Citation
Journal of the American Chemical Society, 2011; 133(45):18272-18279
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Claire M. Weekley, Jade B. Aitken, Stefan Vogt, Lydia A. Finney, David J. Paterson, Martin D. de Jonge, Daryl L. Howard, Paul K. Witting, Ian F. Musgrave and Hugh H. Harris
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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.
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Copyright © 2011 American Chemical Society