title: Gambogic acid inhibits TNF-α-induced invasion of human prostate cancer PC3 cells in vitro through PI3K/Akt and NF-κB signaling pathways.
abstract: OBJECTIVE
  To investigate the mechanisms underlying the inhibitory effect of gambogic acid (GA) on TNF-α-induced metastasis of human prostate cancer PC3 cells in vitro.
  
  
  METHODS
  TNF-α-mediated migration and invasion of PC3 cells was examined using migration and invasion assays, respectively. NF-κB transcriptional activity and nuclear translocation were analyzed with luciferase reporter gene assays, immunofluorescence assays and Western blots. The ability of p65 to bind the promoter of Snail, an important mesenchymal molecular marker, was detected using a chromatin immunoprecipitation (ChIP) assay. After treatment with Snail-specific siRNA, the expression of invasiveness-associated genes was measured using quantitative real-time PCR and Western blot.
  
  
  RESULTS
  GA significantly inhibited the viability of PC3 cells at 1-5 μmol/L, but did not produce cytotoxic effect at the concentrations below 0.5 μmol/L. GA (0.125-0.5 μmol/L) dose-dependently inhibited the migration and invasion of PC3 cells induced by TNF-α (10 ng/mL). Moreover, the TNF-α-mediated activation of phosphatidylinositol-3-OH kinase/protein kinase B (PI3K/Akt) and NF-κB pathways was suppressed by GA (0.5 μmol/L). Furthermore, this anti-invasion effect of GA was associated with regulation of Snail. Snail expression was significantly down-regulated by treatment with GA (0.5 μmol/L) in the TNF-α-stimulated PC3 cells.
  
  
  CONCLUSIONS
  GA inhibits TNF-α-induced invasion of PC3 cells via inactivation of the PI3K/Akt and NF-κB signaling pathways, which may offer a novel approach for the treatment of human prostate cancer.
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lü
authors.forename: Dong
authors.initials: D
authors.lastname: Tang
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Lu-qi
authors.initials: LQ
authors.lastname: Huang
authors.forename: Guo-song
authors.initials: GS
authors.lastname: Jiang
authors.forename: Xing-yuan
authors.initials: XY
authors.lastname: Xiao
authors.forename: Fu-qing
authors.initials: FQ
authors.lastname: Zeng
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D029760:Garcinia / Q000737:chemistry; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000276:immunology*; D009361:Neoplasm Invasiveness / Q000276:immunology / Q000517:prevention & control*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; C052659:gambogic acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt