title: Induction of cytotoxicity and apoptosis in human gastric cancer cell SGC-7901 by isovaltrate acetoxyhydrin isolated from Patrinia heterophylla bunge involves a mitochondrial pathway and G2/M phase cell cycle arrest.
abstract: BACKGROUND
  Our previous study demonstrated cytotoxicity of a crude extract from Patrinia heterophylla Bunge (PHEB). In the present study, we aimed to investigate the effects of isovaltrate acetoxyhydrin (IA) isolated from PHEB on the gastric cancer cell SGC-7901, in order to explore a potential treatment for gastric cancer.
  
  
  METHODS
  MTT assays were employed to determine the effects of IA on cell vitality and proliferation, with monitoring of cell morphology changes and examination of apoptosis with Annexin V-PI staining. Flow cytometry was used to assess cell cycle progression and mitochondrial membrane potential. The activity of caspase 3, 9 was evaluated by spectrophotometry, and the protein levels of Bax, Bcl2 and Cyclin B1 were analyzed with Western blotting of total proteins extracted from cultured cells.
  
  
  RESULTS
  The results demonstrated direct toxicity of IA towards SGC-7901 cells. Evidence of apoptosis included blebbing and chromatin condensation. Annexin V-PI assays revealed early apoptosis, involving rapid depolarization of mitochondrial membranes and activity of caspase 3, 9 signaling pathways. Western blotting showed that Bcl2 and Bax proteins was down- and up-regulated, respectively, and cyclin B1 was up-regulated. Cell cycle analysis further indicated that IA could induce G2/M phase arrest in SGC-7901 cells.
  
  
  CONCLUSIONS
  In conclusion, we believe that IA induces apoptosis of SGC-7901 cells, therefore providing a potential therapeutic agent for treatment of gastric cancer.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China E-mail : zrs789@hotmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yi-Qi
authors.initials: YQ
authors.lastname: Wang
authors.forename: Ru-Bin
authors.initials: RB
authors.lastname: Cheng
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Li-tao
authors.initials: LT
authors.lastname: Jia
authors.forename: Ru-Song
authors.initials: RS
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D053453:Caspase 9 / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D056744:Cyclin B1 / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics; D032405:Patrinia / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D056744:Cyclin B1; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9