title: Oxidative stress mediates apoptotic effects of ascorbate and dehydroascorbate in human Myelodysplasia cells in vitro.
abstract: The Myelodysplastic Syndromes are stem cell heterogeneous disorders characterized by peripheral cytopenias and hypercellular bone marrow, which can evolute to acute leukaemia. Vitamin C can act as an antioxidant, ascorbic acid (AA) donates two electrons and becomes oxidized to dehydroascorbic acid (DHA). Under physiological conditions, vitamin C predominantly exists in its reduced (AA) form but also exists in trace quantities in the oxidized form (DHA). This study evaluates the therapeutic potential of vitamin C in Myelodysplastic Syndromes (MDSs). F36P cells (MDS cell line) were treated with ascorbate and dehydroascorbate alone and in combination with cytarabine. Cell proliferation and viability were assessed by trypan blue assay and cell death was evaluated by optical microscopy and flow cytometry. The role of reactive oxygen species, mitochondrial membrane potential, BAX, BCL-2 and cytochrome C were also assessed. Vitamin C decreases cell proliferation and viability in a concentration, time and administration dependent-manner inducing cell death by apoptosis, which was shown to be associated to an increased in superoxide production, mitochondrial membrane depolarization. These compounds modulate BCL-2, BAX and cytochrome C release. These results suggest that vitamin C induces cell death trough apoptosis in F36P cells and may be a new therapeutic approach in Myelodysplasia.
authors.affiliation: Applied Molecular Biology and Hematology University Clinic, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Gonçalves
authors.forename: Vera
authors.initials: V
authors.lastname: Alves
authors.forename: Teresa
authors.initials: T
authors.lastname: Silva
authors.forename: Cristina
authors.initials: C
authors.lastname: Carvalho
authors.forename: Catarina Resende de
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Ana Bela
authors.initials: AB
authors.lastname: Sarmento-Ribeiro
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D003683:Dehydroascorbic Acid / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D009190:Myelodysplastic Syndromes / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D002374:Catalase; D013482:Superoxide Dismutase; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid