title: Selenium compounds induced ROS-dependent apoptosis in myelodysplasia cells.
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.
authors.affiliation: Applied Molecular Biology, University Clinic of Haematology and Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Gonçalves
authors.forename: André
authors.initials: A
authors.lastname: Barbosa-Ribeiro
authors.forename: Vera
authors.initials: V
authors.lastname: Alves
authors.forename: Teresa
authors.initials: T
authors.lastname: Silva
authors.forename: Ana Bela
authors.initials: AB
authors.lastname: Sarmento-Ribeiro
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018036:Selenium Compounds / Q000494:pharmacology*; D012645:Selenomethionine / Q000494:pharmacology; D018038:Sodium Selenite / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; D051028:bcl-2-Associated X Protein; D003561:Cytarabine; D013481:Superoxides; D012645:Selenomethionine; D053148:Caspase 3; D018038:Sodium Selenite