Abstract
Several authors have demonstrated the chemoprotective and anti-carcinogenic role of selenium. However, the therapeutic potential of selenium in myelodysplastic syndrome (MDS) as single agent and as co-adjuvant of the current therapies has not been previously studied. Sodium selenite and selenomethionine, alone and in combination with cytarabine, induce a decrease in cell viability in a time-, dose- and administration-dependent manner inducing cell death by apoptosis in F36P cells (MDS cell line). These compounds increased superoxide production and induced mitochondrial membrane depolarization. The increase in BAX/BCL-2 ratio and in the activated caspase 3 expression levels, the decrease in mitochondria membrane potential, as well as the increase in superoxide production, supports the mitochondria contribution on selenium-induced apoptosis. These findings suggest that selenium may offer a new therapeutic approach in myelodysplastic syndrome in monotherapy and/or as co-adjuvant therapy to conventional anti-carcinogenic.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimetabolites, Antineoplastic / pharmacology
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Apoptosis / drug effects*
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Caspase 3 / metabolism
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Cell Line
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Cell Proliferation / drug effects*
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Cell Survival / drug effects
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Cytarabine / pharmacology
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Dose-Response Relationship, Drug
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Drug Synergism
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Flow Cytometry
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Humans
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Membrane Potential, Mitochondrial / drug effects
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Membrane Potential, Mitochondrial / physiology
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Mitochondria / drug effects
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Mitochondria / metabolism
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Mitochondria / physiology
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Myelodysplastic Syndromes / drug therapy
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Myelodysplastic Syndromes / metabolism
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Myelodysplastic Syndromes / pathology
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Reactive Oxygen Species / metabolism*
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Selenium Compounds / pharmacology*
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Selenomethionine / pharmacology
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Sodium Selenite / pharmacology
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Superoxides / metabolism
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bcl-2-Associated X Protein / metabolism
Substances
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Antimetabolites, Antineoplastic
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BAX protein, human
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Proto-Oncogene Proteins c-bcl-2
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Reactive Oxygen Species
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Selenium Compounds
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bcl-2-Associated X Protein
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Cytarabine
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Superoxides
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Selenomethionine
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Caspase 3
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Sodium Selenite