title: Curcumin suppresses vasculogenic mimicry capacity of hepatocellular carcinoma cells through STAT3 and PI3K/AKT inhibition.
abstract: BACKGROUND
  Vasculogenic mimicry (VM) refers to the process in which highly invasive cancer cells mimic endothelial cells by forming blood channels. In the present study, we investigated the effect of curcumin, a natural product from turmeric, on VM of SK-Hep-1 human hepatocellular carcinoma (HCC) cells.
  
  
  METHODS
  In vitro VM, cell migration, and matrix metalloproteinase-9 (MMP9) production of HCC cells were determined by Matrigel tube formation assay, Transwell cell migration assay, and gelatin zymography, respectively. Effects of curcumin on AKT, signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB) signaling pathways were determined by immunoblot analysis.
  
  
  RESULTS
  At non-cytotoxic concentrations, curcumin inhibited VM, reduced cell migration and MMP9 production of the HCC cells. Further study revealed that the anti-VM effect of curcumin was due to inhibition of AKT and STAT3 phosphorylation, as confirmed by specific inhibitors.
  
  
  CONCLUSIONS
  Curcumin presents proven potential as an anti-VM agent in HCC cells, through down-regulation of STAT3 and AKT signaling pathways.
authors.affiliation: Laboratory of Biochemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Laksi, Bangkok 10210, Thailand. kriengsak@cri.or.th.
authors.forename: Khajeelak
authors.initials: K
authors.lastname: Chiablaem
authors.forename: Kriengsak
authors.initials: K
authors.lastname: Lirdprapamongkol
authors.forename: Siriporn
authors.initials: S
authors.lastname: Keeratichamroen
authors.forename: Rudee
authors.initials: R
authors.lastname: Surarit
authors.forename: Jisnuson
authors.initials: J
authors.lastname: Svasti
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003474:Curcumin; D020780:Matrix Metalloproteinase 9; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D050796:STAT3 Transcription Factor
keywords: Curcumin; antimetastatic; hepatocellular carcinoma; natural products; vasculogenic mimicry