title: Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma.
abstract: OBJECTIVE
  Osteosarcoma is the second highest cause of cancer-related death in children and adolescents. Majority of osteosarcoma patients (90%) show metastasis. Previous reports revealed that osthole showed antitumor activities via induction of apoptosis and inhibition of proliferation. However, the potential effects and detailed molecular mechanisms involved remained unclear.
  
  
  METHODS
  Cell viability was analyzed by MTT assay in osteosarcoma cell lines MG-63 and SAOS-2. Cell cycle was detected by flow cytometry. The effects of migration and invasion were evaluated by wound healing assay and transwell assays. Moreover, the level of proteins expression was determined by Western blot.
  
  
  RESULTS
  The cell viability of MG63 and SAOS-2 were markedly inhibited by osthole in a dose- and time-dependent manner. Cell cycle was arrested and the ability of migration and invasion was obviously reduced when cells were exposed to osthole. Moreover, enzymes involved in PTEN/Akt pathway were regulated such as PTEN and p-Akt proteins. Furthermore, osthole inhibited the tumor growth in vivo.
  
  
  CONCLUSIONS
  Our study unraveled, for the first time, the ability of osthole to suppress osteosarcoma and elucidated the regulation of PTEN/Akt pathway as a signaling mechanism for the anti-tumor action of osthole. These findings indicate that osthole may represent a novel therapeutic strategy in the treatment of osteosarcoma.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: Yingzhun
authors.initials: Y
authors.lastname: Chen
authors.forename: Tianhua
authors.initials: T
authors.lastname: Liu
authors.forename: Yanli
authors.initials: Y
authors.lastname: Peng
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Bi
authors.forename: Tianyi
authors.initials: T
authors.lastname: Liu
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Liu
authors.forename: Hongli
authors.initials: H
authors.lastname: Shan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C046627:osthol