Exposure of human leukemia NB4 cells to increasing concentrations of selenite switches the signaling from pro-survival to pro-apoptosis

Guan, Lina; Han, Bingshe; Li, Jian; Li, Zhushi; Huang, Fang; Yang, Yang; Xu, Caimin

doi:10.1007/s00277-008-0676-4

Cited by 29 publications

(31 citation statements)

References 31 publications

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“…Serum selenium concentrations provide prognostic implications because they can serve as a positive indicator for predicting effective dosage levels, optimum delivery routes, treatment response, and long-term survival [82]. The biology of cancer cells is modified by selenium based on it’s capacity to 1) induce apoptosis in doxorubicin-resistant lung small-cell carcinoma (selenite 10 μM) [46]; 2) promote severe ER stress (leukemia cell types) [83]; 3) reduce vitality of multidrug-resistant leukemia (selenitetriglycerides 10 μg/ml to 40 μg/ml) [84]; and 4) influence Fas signaling in MCF-7 mamary carcinoma in the presence of doxorubicin (methylseleninate 5 μM) [43].…”

Section: Discussionmentioning

confidence: 99%

Epirubicin-[Anti-HER2/neu] Synthesized with an Epirubicin-(C13-imino)-EMCS Analog: Anti-Neoplastic Activity against Chemotherapeutic-Resistant SKBr-3 Mammary Carcinoma in Combination with Organic Selenium

Coyne¹,

Jones²,

Syguła³

et al. 2011

JCT

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Purpose Discover the anti-neoplastic efficacy of epirubicin-(C13-imino)-[anti-HER2/neu] against chemotherapeutic-resistant SKBr-3 mammary carcinoma and delineate the capacity of selenium to enhance it’s cytotoxic anti-neoplastic potency. Methods In molar excess, EMCH was combined with epirubicin to create a covalent epirubicin-(C13-imino)-EMCH-maleimide intermediate with sulfhydryl-reactive properties. Monoclonal immunoglobulin selective for HER2/neu was then thiolated with 2-iminothiolane at the terminal ε-amine group of lysine residues. The sulfhydryl-reactive epirubicin-(C13-imino)-EMCH intermediate was then combined with thiolated anti-HER2/neu monoclonal immunoglobulin. Western-blot analysis was utilized to characterize the molecular weight profiles while binding of epirubicin-(C13-imino)-[anti-HER2/neu] to membrane receptors was determined by cell-ELISA utilizing populations of SKBr-3 mammary carcinoma that highly over-expresses HER2/neu complexes. Anti-neoplastic potency of epirubicin-(C13-imino)-[anti-HER2/neu] between the epirubicin-equivalent concentrations of 10−12 M and 10−7 M was determined by vitality staining analysis with and without the presence of selenium (5 μM). Results Epiribucin-(C13-imino)-[anti-HER2/neu] between epirubicin-equivalent concentrations of 10−8 M to 10−7 M consistently evoked higher anti-neoplastic potency than “free” non-conjugated epirubicin which corresponded with previous investigations utilizing epirubicin-(C3-amide)-[anti-HER2/neu] and epirubicin-(C3-amide)-[anti-EGFR]. Selenium at 5 mM consistently enhanced the cytotoxic anti-neoplastic potency of epirubicin-(C13-imino)-[anti-HER2/neu] at epirubicin equivalent concentrations (10–12 to 10–7 M). Conclusions Epirubicin-(C13-imino)-[anti-HER2/neu] is more potent than epirubicin against chemotherapeutic-resistant SKBr-3 mammary carcinoma and selenium enhances epirubicin-(C13-imino)-[anti-HER2/neu] potency. The methodology applied for synthesizing epirubicin-(C13-imino)-[anti-HER2/neu] is relatively time convenient and has low instrumentation requirements.

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Section: Discussionmentioning

confidence: 99%

Epirubicin-[Anti-HER2/neu] Synthesized with an Epirubicin-(C13-imino)-EMCS Analog: Anti-Neoplastic Activity against Chemotherapeutic-Resistant SKBr-3 Mammary Carcinoma in Combination with Organic Selenium

Coyne¹,

Jones²,

Syguła³

et al. 2011

JCT

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“…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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confidence: 99%

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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“…On the other hand, use of selenium-cystine (as diseleno-dialanine) in leukemic patients decreased total leukocyte count, immature leukocytes in CML and AML patients (17). Anti-leukemic effect of sodium selenite (Na 2 SeO 3 ) was suggested to activate p53 to cause apoptosis (18–24). However, the mechanism by which selenium activates p53 is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Selenium Suppresses Leukemia through the Action of Endogenous Eicosanoids

et al. 2014

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Eradicating cancer stem-like cells (CSC) may be essential to fully eradicate cancer. Metabolic changes in CSC could hold a key to their targeting. Here we report that the dietary micronutrient selenium can trigger apoptosis of CSC derived from chronic or acute myelogenous leukemias when administered at supraphysiological but non-toxic doses. In leukemia CSC, selenium treatment activated ATM-p53-dependent apoptosis accompanied by increased intracellular levels of reactive oxygen species. Importantly, the same treatment did not trigger apoptosis in hematopoietic stem cells. Serial transplantation studies with BCR-ABL-expressing CSC revealed that the selenium status in mice was a key determinant of CSC survival. Selenium action relied upon the endogenous production of the cyclooxygenase-derived prostaglandins Δ12-PGJ2 and 15d-PGJ2. Accordingly, non-steroidal anti-inflammatory drugs and NADPH oxidase inhibitors abrogated the ability of selenium to trigger apoptosis in leukemia CSC. Our results reveal how selenium-dependent modulation of arachidonic acid metabolism can be directed to trigger apoptosis of primary human and murine CSC in leukemia.

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Exposure of human leukemia NB4 cells to increasing concentrations of selenite switches the signaling from pro-survival to pro-apoptosis

Cited by 29 publications

References 31 publications

Epirubicin-[Anti-HER2/neu] Synthesized with an Epirubicin-(C13-imino)-EMCS Analog: Anti-Neoplastic Activity against Chemotherapeutic-Resistant SKBr-3 Mammary Carcinoma in Combination with Organic Selenium

Epirubicin-[Anti-HER2/neu] Synthesized with an Epirubicin-(C13-imino)-EMCS Analog: Anti-Neoplastic Activity against Chemotherapeutic-Resistant SKBr-3 Mammary Carcinoma in Combination with Organic Selenium

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

Selenium Suppresses Leukemia through the Action of Endogenous Eicosanoids

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