title: Comparative proteomic analysis of anti-cancer mechanism by periplocin treatment in lung cancer cells.
abstract: BACKGROUND
  Periplocin is used for treatment of rheumatoid arthritis, reinforcement of bones and tendons, palpitations or shortness of breath and lower extremity edema in traditional medicine. Our previous findings suggested that periplocin could inhibit the growth of lung cancer both in vitro and in vivo. But the biological processes and molecular pathways by which periplocin induces these beneficial effects remain largely undefined.
  
  
  METHODS
  To explore the molecular mechanisms of periplocin involved in anti-cancer activity, in the present study the protein profile changes of human lung cancer cell lines A549 in response to periplocin treatment were investigated using the proteomics approaches (2-DE combined with MS/MS). Western blot was employed to verify the changed proteins. Interactions between changed proteins were analyzed by STRING.
  
  
  RESULTS
  29 down-regulated protein species named GTP-binding nuclear protein Ran (RAN), Rho GDP-dissociation inhibitor 1 (ARHGDIA), eukaryotic translation initiation factor 5A-1 (EIF5A) and Profilin-1(PFN1), and 10 up-regulated protein species named Heat shock cognate 71 kDa protein (HSPA8),10 kDa heat shock protein (HSPE1), and Cofilin-1(CFL-1) were identified. Among them, GTP-binding nuclear protein Ran (RAN) and Rho GDP-dissociation inhibitor 1 (ARHGDIA) were the most significantly changed (over tenfold). The proteasome subunit beta type-6 (PSMB6), ATP synthase ecto-α-subunit (ATP5A1), Aldehyde dehydrogenase 1 (ALDH1) and EIF5A were verified by immunoblot assays to be dramatically down-regulated. By STRING bioinformatics analysis revealing interactions and signaling networks it became apparent that the proteins changed they are primarily involved in transcription and proteolysis.
  
  
  CONCLUSIONS
  Periplocin inhibited growth of lung cancer by down-regulating proteins, such as ATP5A1, EIF5A, ALDH1 and PSMB6. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of periplocin on lung cancer cells.
authors.affiliation: Department of Radiation Oncology, Naval General Hospital of PLA, Beijing, China.
authors.forename: Zejun
authors.initials: Z
authors.lastname: Lu
authors.forename: Qi
authors.initials: Q
authors.lastname: Song
authors.forename: Jinliang
authors.initials: J
authors.lastname: Yang
authors.forename: Xiangfei
authors.initials: X
authors.lastname: Zhao
authors.forename: Xinhong
authors.initials: X
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Jingbo
authors.initials: J
authors.lastname: Kang
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D020543:Proteome / Q000096:biosynthesis*; D040901:Proteomics; D012503:Saponins / Q000494:pharmacology*
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome; D012503:Saponins; C502381:periplocin