title: Antiproliferative and antitumor effects of azacitidine against the human myelodysplastic syndrome cell line SKM-1.
abstract: BACKGROUND
  The myelodysplastic syndromes (MDS) are a group of stem cell disorders characterized by dysplasia of one or more hematopoietic cell lineages and a risk of progression to acute myeloid leukemia. The cytidine analog azacitidine (Vidaza), a hypomethylating agent, improves survival in patients with MDS, but its mechanism of action is not well understood.
  
  
  METHODS
  The effects of azacitidine on the MDS-derived cell line SKM-1 were investigated by DNA methylation assay, cell proliferation assay, and a subcutaneous xenograft mouse model.
  
  
  RESULTS
  Azacitidine and decitabine induced hypomethylation of the tumor suppressor gene cyclin-dependent kinase 4 inhibitor B (CDKN2B) in SKM-1 cells, whereas the deoxycytidine analog cytarabine did not. Azacitidine and decitabine also inhibited SKM-1 cell growth in vitro. In the mouse xenograft model, azacitidine significantly suppressed tumor growth.
  
  
  CONCLUSIONS
  Inhibition of DNA methyltransferase by azacitidine contributes to its antiproliferative and antitumor effects against SKM-1 cells and may explain its clinical efficacy in MDS.
authors.affiliation: Exploratory Department, Discovery Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan. s.kimura@po.nippon-shinyaku.co.jp
authors.forename: Sachie
authors.initials: S
authors.lastname: Kimura
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kuramoto
authors.forename: Junko
authors.initials: J
authors.lastname: Homan
authors.forename: Haruna
authors.initials: H
authors.lastname: Naruoka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ego
authors.forename: Masaki
authors.initials: M
authors.lastname: Nogawa
authors.forename: Seishi
authors.initials: S
authors.lastname: Sugahara
authors.forename: Haruna
authors.initials: H
authors.lastname: Naito
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019175:DNA Methylation; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D001374:Azacitidine