title: Synthetic Terrein Inhibits Progression of Head and Neck Cancer by Suppressing Angiogenin Production.
abstract: OBJECTIVE
  Head and neck cancers are the fifth most common cancer type worldwide, affecting more than half a million patients annually. Development of effective therapeutic drugs is, therefore, required for this type of disease. This study assessed the effects of synthetic terrein on head and neck cancer.
  
  
  METHODS
  Synthetic terrein was prepared by using the modified Altenhach's procedure. The effect of synthetic terrein on cell proliferation of head and neck cancer cells and HUVECs was assessed. Angiogenin secretion and ribosome biogenesis were examined by ELISA and silver staining of the nucleolar organizer region. A mouse xenograft model was prepared by inoculating mice with suspensions of cells of the human head and neck cancer cell line OSC-19 subcutaneously into the dorsal region of each mouse. Ki-67, CD31 and angiogenin expression in xenografted tumors was examined by immunohistochemistry.
  
  
  RESULTS
  Synthetic terrein inhibited the growth of various head and neck cancer cells. In addition, an in vivo experiment revealed that synthetic terrein inhibited a xenograft tumor growth in athymic mice. Immunohistochemical analysis revealed that expression of Ki-67, CD31 and ANG was down-regulated in synthetic terrein-treated tumors, compared to controls. Synthetic terrein suppressed the ANG secretion and ribosome biogenesis in cancer cells, and cell proliferation in vascular endothelial cells.
  
  
  CONCLUSIONS
  The mechanism underlying the anti-tumor effects of synthetic terrein against head and neck cancer consists of the inhibition of both tumor cell proliferation and angiogenesis via the suppression of ANG production.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Shibata
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan sibaragi@md.okayama-u.ac.jp.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ibaragi
authors.affiliation: Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mandai
authors.affiliation: Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Toki
authors.initials: T
authors.lastname: Tsumura
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kishimoto
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Okui
authors.affiliation: School of Dentistry & Health Sciences, Charles Sturt University, Orange, NSW, Australia.
authors.forename: Nur Mohammad Monsur
authors.initials: NM
authors.lastname: Hassan
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shimo
authors.affiliation: Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Omori
authors.affiliation: Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, U.S.A.
authors.forename: Guo-Fu
authors.initials: GF
authors.lastname: Hu
authors.affiliation: Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Takashiba
authors.affiliation: Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Suga
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sasaki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology*; D018450:Disease Progression; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D003517:Cyclopentanes; C439087:terrein; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
keywords: Synthetic terrein; angiogenesis; cell proliferation; head and neck cancer; squamous cell carcinoma