title: Garcinol exhibits anti-proliferative activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells.
abstract: BACKGROUND
  Colorectal cancer is the fourth leading cause of death. Various natural compounds are known to have antitumor properties. Garcinol, a polyisoprenylated benzophenone, has antioxidant and anti-inflammatory properties. In the current study, we investigated the anticancer activity of garcinol on human colorectal adenocarcinoma cell line (HT-29) human colon cancer cells.
  
  
  METHODS
  HT-29 cells were treated with various concentrations of garcinol for 24 h. The effect of garcinol on HT-29 cells proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; the mRNA expression of microsomal prostaglandin E synthase-1 (mPGES-1), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) were examined by quantitative real-time polymerase chain reaction; apoptosis was detected by proportion of sub-G1 cell; caspase 3 activity and prostaglandin E2 (PGE2) level were determined by enzyme-linked immunosorbent assay and HT-29 cells migration was assessed using scratch test.
  
  
  RESULTS
  Garcinol preconditioning markedly decreased the expression of mPGES-1, HIF-1α, VEGF, CXCR4, MMP-2, and MMP-9. The proportion of cells in sub-G1 phase and caspase 3 activity were increased by garcinol treatment whereas the cell proliferation, PGE2 level, and cell migration were decreased in these cells, compared to the control group.
  
  
  CONCLUSIONS
  Our findings suggest that garcinol plays a critical role in elevating apoptosis and inhibiting HT-29 cells proliferation, angiogenesis, and invasion by suppressing the mPGES-1/PGE2/HIF-1α signaling pathways.
authors.affiliation: Research center for molecular medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: T
authors.initials: T
authors.lastname: Ranjbarnejad
authors.affiliation: Research center for molecular medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Saidijam
authors.affiliation: Research center for molecular medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: M Sadat
authors.initials: MS
authors.lastname: Tafakh
authors.affiliation: Research center for molecular medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Pourjafar
authors.affiliation: Research center for molecular medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Talebzadeh
authors.affiliation: Research center for molecular medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: R
authors.initials: R
authors.lastname: Najafi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D019073:HT29 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008861:Microsomes / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D000071876:Prostaglandin-E Synthases / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019718:Receptors, CXCR4; D013729:Terpenes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D053148:Caspase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; C054597:garcinol
keywords: Garcinol; colorectal cancer; microsomal prostaglandin E synthase-1; prostaglandin E2