title: Sodium selenite inhibits leukemia HL-60 cell proliferation and induces cell apoptosis by enhancing the phosphorylation of JNK1 and increasing the expression of p21 and p27.
abstract: Selenium is an essential trace element and has shown chemopreventive or therapeutic activities on human solid cancers; however, whether it has anticancer effects on leukemia has not yet been elucidated. The present study was designed to determine the role of selenium on HL-60 human promyelocytic leukemia cells. We found that 100 nM of sodium selenite (Se) had no significant effects on cell proliferation, apoptosis and the cell cycle; however, a higher concentration of 250 nM of Se significantly inhibited cell proliferation, promoted apoptosis and induced cell cycle arrest at the S phase after 48 h of treatment (P<0.05), thus demonstrating the anticancer activities of selenium in leukemia. However, the decrease in c-Jun NH2-terminal kinase 1 (JNK1) expression by targeting JNK1 using small interfering RNA attenuated the inhibitory effects of Se on cell proliferation and the induction of apoptosis. Mechanistic studies showed that the anticancer activities of Se were associated with the enhanced phosphorylation of JNK1 and the increased expression of the cell cycle regulators, p21 and p27, as well as the downregulation of cyclin D1. Our data provide further evidence that the appropriate concentration of selenium has therapeutic potential in leukemia.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P.R. China.
authors.forename: Sun
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Immunology, Xinxiang Medical University, Xinxiang, Henan, P.R. China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P.R. China.
authors.forename: Youmei
authors.initials: Y
authors.lastname: Zi
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P.R. China.
authors.forename: Cui
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P.R. China.
authors.forename: Man
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Mengtao
authors.initials: M
authors.lastname: Xing
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, Henan, P.R. China.
authors.forename: Wancai
authors.initials: W
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D018038:Sodium Selenite / Q000494:pharmacology*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048031:JNK Mitogen-Activated Protein Kinases; D018038:Sodium Selenite