title: Decitabine inhibits tumor cell proliferation and up-regulates e-cadherin expression in Epstein-Barr virus-associated gastric cancer.
abstract: The present study investigated the effect of a DNA demethylating agent, decitabine, against Epstein-Barr virus-associated gastric cancer (EBVaGC). Decitabine inhibited cell growth and induced G2/M arrest and apoptosis in EBVaGC cell lines. The expression of E-cadherin was up-regulated and cell motility was significantly inhibited in the cells treated with decitabine. The promoter regions of p73 and RUNX3 were demethylated, and their expression was up-regulated by decitabine. They enhanced the transcription of p21, which induced G2/M arrest and apoptosis through down-regulation of c-Myc. Decitabine also induced the expression of BZLF1 in SNU719. Induction of EBV lytic infection was an alternative way to cause apoptosis of the host cells. This study is the first report to reveal the effectiveness of a demethylating agent in inhibiting tumor cell proliferation and up-regulation of E-cadherin in EBVaGC. J. Med. Virol. 89:508-517, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Laboratory Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nishikawa
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suehiro
authors.affiliation: Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015820:Cadherins / Q000096:biosynthesis*; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D000077209:Decitabine; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D006801:Humans; D013274:Stomach Neoplasms / Q000473:pathology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D015820:Cadherins; D000077209:Decitabine; D001374:Azacitidine
keywords: Epstein-Barr virus; apoptosis/cell death; gastrointestinal analysis; tumor suppressor genes