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.

Estimating Intestinal Absorption of Inorganic and Organic Selenium Compounds by in Vitro Flux and Biotransformation Studies in Caco-2 Cells and ICP-MS Detection

“…This lack of transformation of the selenoamino acids in Caco-2 cells is in agreement with SeMet and MeSeCys being substrates of amino acid transporters [17]. The same pattern has been observed in studies on biotransformations in the prostate carcinoma (PC-3) and T cell leukemia (Jurkat) cell lines [28]. In addition, size exclusion chromatography revealed that a selenium-containing protein was formed in the cell lysate (Fig.…”

Sodium selenite-induced activation of DAPK promotes autophagy in human leukemia HL60 cells

“…Sodium selenite is commonly used as a source of selenium in biological research. Accumulating evidences confirmed the application of selenite in studies of cell proliferation and cancer (3,4). Previous results suggested supranutritional doses of selenite promoted cell death through mitochondria-or ER stress-mediated apoptotic pathway in human leukemia cell lines (5,6).…”

Substituted diaryl diselenides: Cytotoxic and apoptotic effect in human colon adenocarcinoma cells

“…The (3-CF 3 C 6 H 4 Se) and (4-MeOC 6 H 4-Se) compounds induced cytotoxicity and alterations in cell morphology in HT-29 cells in a dose-dependent manner: 20 μM (24.4 vs. 65.2%), 40 μM (81.8 vs. 81.7%) and 80 μM (91.2 vs. 96.1%), respectively. A recent study evaluated the ability of different selenium compounds (selenate, selenite, MeSeA, MeSeCys and SeMet) to induce cell death in HT-29 cells (Lunøe et al, 2011). The most effective compound was selenite, an inorganic selenium, the percentage of cell death was 21 (10 μM) and 39% (100 μM), followed by two organic selenium compounds, MeSeA (methylseleninic acid) 2 (10 μM) and 14% (100 μM), and MeSeCys (Se-methylselenocysteine) 3% (100 μM).…”