title: Potent effects of dioscin against gastric cancer in vitro and in vivo.
abstract: BACKGROUND
  We previously reported the effect of dioscin on human gastric carcinoma SGC-7901 cells, but its effects on other gastric cancers are still unknown.
  
  
  OBJECTIVE
  The present paper aimed to demonstrate the activity of dioscin against human gastric carcinoma MGC-803 and MKN-45.
  
  
  METHODS
  In our study, MGC-803 and MKN-45 cells were used to examine the effects of dioscin on human gastric carcinoma in vitro. The effects of dioscin against human gastric carcinoma in vivo were accomplished by the xenografts of MGC-803 cells in BALB/c nude mice.
  
  
  METHODS
  AO/EB and DAPI staining, TEM, single cell gel electrophoresis and flow cytometry assays were used in cell experiments. Then, an iTRAQ-based proteomics approach, DNA and siRNA transfection experiments were carried out for mechanism investigation.
  
  
  RESULTS
  In MGC-803 cells, dioscin caused DNA damage and mitochondrial change, induced ROS generation, Ca(2+) release and cell apoptosis, and blocked cell cycle at S phase. In vivo results showed that dioscin significantly suppressed the tumor growth of MGC-803 cell xenografts in nude mice. In addition, dioscin markedly inhibited cell migration, caused Cytochrome c release and adjusted mitochondrial signal pathway. Then, an iTRAQ-based proteomics approach was carried out and 121 differentially expressed proteins were found, in which five biomarkers associated with cell cycle, apoptosis and migration were evaluated. Dioscin significantly up-regulated the levels of GALR-2 and RBM-3, and down-regulated CAP-1, Tribbles-2 and CliC-3. Furthermore, overexpressed DNA transfection of CAP-1 enhanced cell migration and invasion, which was decreased by dioscin. SiRNA to Tribbles-2 affected the protein levels of Bcl-2, Bax and MAPKs, suggesting that dioscin decreased Tribbles-2 level leading to cell apoptosis.
  
  
  CONCLUSIONS
  Our works confirmed the activity of dioscin against gastric cancer. In addition, this work also provided that dioscin is a new potent candidate for treating gastric cancer in the future.
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pharmaceuticals, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Zheng
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Electronic address: jinyongpeng2014@163.com.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004249:DNA Damage; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects; D020543:Proteome; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D020543:Proteome; D017382:Reactive Oxygen Species; C019357:dioscin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human; D004144:Diosgenin
keywords: Apoptosis; Cell migration; Dioscin; Gastric cancers; Proteomics