title: Epigenetic modulation by methionine deficiency attenuates the potential for gastric cancer cell dissemination.
abstract: BACKGROUND
  Methionine dependency occurs frequently in tumor cells. Here we have investigated the effect of methionine deficiency on metastatic potential of gastric cancer cells in vitro and in vivo.
  
  
  METHODS
  Model of peritoneal carcinomatosis and xenograft was generated by intraperitoneal or subcutaneous implantation of gastric cancer cells in NOD-SCID mice. In comparison to control medium, 3-day culture of MKN45, MKN74, and KATOIII cells in a methionine-deficient medium inhibited cell proliferation, increased the rate of cell apoptosis, and reduced cell adhesion and migration. In the xenograft model induced by implantation of MNK45 and MNK74 cells, two cycles of methionine-deficient diet reduced the tumor growth. Further on, a 10-day cycle of methionine-deficient diet reduced the number of peritoneal nodules in the model of peritoneal carcinomatosis induced by MKN45 cells injection. Finally, a microarray analysis of the methylation of promoter CpG islets demonstrated that methionine deficiency reduced the promoter methylation of E-cadherin whose expression was markedly increased in vivo and in vitro.
  
  
  RESULTS
  In summary, we have provided evidence that a methionine-deficient diet modulates the growth of gastric tumor cells and in vitro deficiency of methionine increased apoptosis and decreased cellular adhesion and migration associated to epigenetic change of E-cadherin gene, in vivo and in vitro.
authors.affiliation: Dipartimento di Scienze Chirurgiche, Radiologiche e Odontostomatologiche, Nuova Facoltà di Medicina e Chirurgia, Sant' Andrea delle Fratte, Perugia, 06132, Italy.
authors.forename: Luigina
authors.initials: L
authors.lastname: Graziosi
authors.forename: Andrea
authors.initials: A
authors.lastname: Mencarelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Renga
authors.forename: Claudio
authors.initials: C
authors.lastname: D'Amore
authors.forename: Angela
authors.initials: A
authors.lastname: Bruno
authors.forename: Chiara
authors.initials: C
authors.lastname: Santorelli
authors.forename: Emanuel
authors.initials: E
authors.lastname: Cavazzoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Cantarella
authors.forename: Emanuele
authors.initials: E
authors.lastname: Rosati
authors.forename: Annibale
authors.initials: A
authors.lastname: Donini
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiorucci
mesh_terms: D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003470:Culture Media / Q000737:chemistry; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008715:Methionine / Q000172:deficiency*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary*; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D015820:Cadherins; D003470:Culture Media; D005819:Genetic Markers; D008715:Methionine