Selenite is a potent cytotoxic agent for human primary AML cells

Olm, Eric; Jönsson-Videsäter, Kerstin; Ribera‐Cortada, Inmaculada; Fernandes, Aristi P.; Eriksson, Lennart C.; Lehmann, Sören; Rundlöf, Anna-Klara; Paul, Christer; Björnstedt, Mikael

doi:10.1016/j.canlet.2009.03.010

Cited by 39 publications

(33 citation statements)

References 41 publications

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“…This phenomenon is explained by the intracellular accumulation of selenite caused by its efficient uptake following cysteine recycling through the cystine/glutamate antiporter and multidrug resistance protein, both of which are frequently overexpressed on tumor cells (38). In addition to this selective uptake, tumor cells have also been shown to be more sensitive to selenite per se, since the intracellular redox cycles between selenide, thiols, and oxygen that cause formation of reactive oxygen species (26) are more pronounced in tumor cells due to their increased levels of thiols compared with normal cells (58).…”

Section: Discussionmentioning

confidence: 99%

“…Because of these selective effects on tumor cells, it would be exciting to explore whether selenite can induce specific downregulation of HLA-E on tumor cells in vivo, while preserving its expression on normal cells and thereby preventing NK cell targeting of normal HLA-E-expressing tissues. Besides its effects on HLA-E, selenite is also an attractive drug candidate because of its other anti-tumor properties, including inhibition of cellular growth and induction of DNA strand breaks leading to apoptosis (35)(36)(37)(38)59). In fact, one recent study showed that low concentrations of selenite were more cytotoxic to primary AML blast cells than were conventional drugs (60), and several other studies have indicated that selenite is especially cytotoxic in tumor cells that are resistant to conventional drugs (34,40).…”

Section: Discussionmentioning

confidence: 99%

“…Low dietary intake of selenium has been associated with an increased incidence of prostate cancer (29), whereas supplementation has been linked to reduced risk for cancers such as skin and liver cancer (30)(31)(32). Interestingly, the inorganic selenium compound selenite (SeO 3 22 ) has been shown to induce apoptosis in a wide range of solid tumor cells (33)(34)(35)(36) and various hematological malignancies (37,38), with a selective cytotoxic effect on malignant cells compared with normal cells (39)(40)(41). Selenite can also hit drug-resistant tumor cells (33,42) and potentiate the effect of some chemotherapeutic drugs (35,43).…”

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Selenite Induces Posttranscriptional Blockade of HLA-E Expression and Sensitizes Tumor Cells to CD94/NKG2A-Positive NK Cells

Enqvist

Nilsonne

Hammarfjord

et al. 2011

The Journal of Immunology

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CD94/NKG2A is an inhibitory receptor that controls the activity of a large proportion of human NK cells following interactions with the nonclassical HLA class Ib molecule HLA-E expressed on target cells. In this study, we show that selenite (SeO32−), an inorganic selenium compound, induces an almost complete loss of cell surface expression of HLA-E on tumor cells of various origins. Selenite abrogated the HLA-E expression at a posttranscriptional level, since selenite exposure led to a dose-dependent decrease in cellular HLA-E protein expression whereas the mRNA levels remained intact. The loss of HLA-E expression following selenite treatment was associated with decreased levels of intracellular free thiols in the tumor cells, suggesting that the reduced HLA-E protein synthesis was caused by oxidative stress. Indeed, HLA-E expression and the level of free thiols remained intact following treatment with selenomethionine, a selenium compound that does not generate oxidative stress. Loss of HLA-E expression, but not of total HLA class I expression, on tumor cells resulted in increased susceptibility to CD94/NK group 2A-positive NK cells. Our results suggest that selenite may be used to potentiate the anti-tumor cytotoxicity in settings of NK cell-based immunotherapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Selenite Induces Posttranscriptional Blockade of HLA-E Expression and Sensitizes Tumor Cells to CD94/NKG2A-Positive NK Cells

Enqvist

Nilsonne

Hammarfjord

et al. 2011

The Journal of Immunology

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“…A recent study by Olm et al (40) indicated that selenite toxicity in cancer cells depended on extracellular reduction by thiols such as cysteine. In our study, the test compounds did not reduce MTT reagent in a cell free system at concentrations up to and including 60 μmol L -1 (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Ebselen Analogues Reduce 2-chloroethyl Ethyl Sulphide Toxicity in A-431 Cells

Pino

Pįętka-Ottlik

Billack

2013

Archives of Industrial Hygiene and Toxicology

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Vesicants are potent blistering agents. The prototype vesicant is sulphur mustard gas, fi rst used in World War I, which still has no effective antidote. We used a mustard gas surrogate 2-chloroethyl ethyl sulphide (CEES) to study the ability of resveratrol (RES) and pterostilbene (PTS), two well-established stilbene antioxidants, ebselen (EB-1), an organoselenium compound, and three EB-1 analogues (EB-2, EB-3, and EB-4) to reduce CEES toxicity in human epidermoid carcinoma cells (A-431). Following a 24-hour incubation of a toxic concentration of CEES (1000 μmol L ) did not decrease cell viability. Treatment with CEES and test antioxidants for 24 h showed that only EB-1 and its analogues EB-2, EB-3, and EB-4 but not the stilbene compounds could rescue the cells from death. EB-1 and EB-4 were the most effective at reducing CEES cytotoxicity and did so in a concentration-dependent manner, while EB-2 and EB-3 demonstrated the least protective effect. In summary, the data described herein indicate that organoselenium antioxidants, especially EB-4, may prove useful as countermeasures to blistering agents.

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“…It occurs naturally in four oxidation states: selenide (-2), elemental selenium (0), selenite (+4) and selenate (+6) states. In a view of Se toxicity, selenite is most potent cytotoxic agent among inorganic forms of selenium [9]. However, the mechanism and aspect responsible for intestinal absorption and distribution of selenite are not clear.…”

Section: Introductionmentioning

confidence: 99%

Absorption and Distribution for Subtoxic Level of Selenite by Vascularly Perfused Small Intestine in Rats

Park¹,

Yoon²,

Kim³

2010

Journal of Life Science

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Intestinally absorptive and distributive aspects of the subtoxic level of selenite in rats were investigated using a double perfusion system. The double-perfusion technique is an in situ, in vitro preparation in which the intestinal lumen and its vasculature are perfused simultaneously. In the previous study, the subtoxic level of sodium selenite was determined to be 1.2 mM through inhibition of 3-0-methyl glucose (3MG) absorption. Thus, the selenite used to identify the intestinally absorptive mechanism of selenite was perfused at a luminal concentration of 1, 10, 50, 100 and 200 μM. Appearance of radiolabeled-Selenium (Se) was identified in three compartments: luminal perfusate, small intestine and vascular perfusate. Dose-response curves for Se in the three compartments indicate that selenite is absorbed by non-mediated passive diffusion. Regarding the distributive aspect, 21.02±3.92% of the total amount of selenite in the lumen was transported into the blood vessels across the small intestine. However, 4.75±1.75% of the total amount of selenite in the lumen is retained by the small intestine. Therefore, a total of 25.67±4.46% of the test dose was taken up from the luminal perfusate.

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Selenite is a potent cytotoxic agent for human primary AML cells

Cited by 39 publications

References 41 publications

Selenite Induces Posttranscriptional Blockade of HLA-E Expression and Sensitizes Tumor Cells to CD94/NKG2A-Positive NK Cells

Selenite Induces Posttranscriptional Blockade of HLA-E Expression and Sensitizes Tumor Cells to CD94/NKG2A-Positive NK Cells

Ebselen Analogues Reduce 2-chloroethyl Ethyl Sulphide Toxicity in A-431 Cells

Absorption and Distribution for Subtoxic Level of Selenite by Vascularly Perfused Small Intestine in Rats

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