title: Pigment epithelial-derived factor inhibits c-FLIP expression and assists ciglitazone-induced apoptosis in hepatocellular carcinoma.
abstract: BACKGROUND
  Pigment epithelial-derived factor (PEDF) displays its antiangiogenicity by mechanisms partly involving suppression of the cellular FADD-like IL-1β-converting enzyme (FLICE)/caspase-8-inhibitory protein (c-FLIP) expression in endothelial cells. c-Jun NH(2)-terminal kinases (JNKs) regulate c-FLIP expression in endothelial cells. The effect of PEDF on other cells remains unclear.
  
  
  METHODS
  c-FLIP expression was assessed by semi-quantitative reverse transcriptase (RT)-PCR and immunoblotting. Pharmacological inhibitors were used to examine the involvement of PEDF signaling.
  
  
  RESULTS
  PEDF can also down-regulate c-FLIP expression in hepatoma cell line SK-Hep-1. PEDF induced p38 kinase phosphorylation in SK-Hep-1 cells. The effect of PEDF on c-FLIP expression was attenuated by p38 kinase inhibitor, but not JNK inhibitor. In addition, PEDF pretreatment significantly increased the sensitivity of SK-Hep-1 cells to procaspase-8 cleavage and apoptosis induced by ciglitazone.
  
  
  CONCLUSIONS
  PEDF-induced p38 signaling causes c-FLIP down-regulation in SK-Hep-1. We postulate PEDF has a novel effect on apoptotic inducible activity in hepatoma cells.
authors.affiliation: Department of Ophthalmology, Chang Gang Memorial Hospital, Chia-Yi County, Taiwan, Republic of China.
authors.forename: Li-Ju
authors.initials: LJ
authors.lastname: Lai
authors.forename: Tsung-Chuan
authors.initials: TC
authors.lastname: Ho
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D053181:Caspase 8 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053181:Caspase 8; D005136:Eye Proteins; D007004:Hypoglycemic Agents; D048670:MAP Kinase Kinase 4; D009414:Nerve Growth Factors; D047495:PPAR gamma; D012333:RNA, Messenger; D015843:Serpins; D045162:Thiazolidinediones; D048051:p38 Mitogen-Activated Protein Kinases; D000099174:Pigment Epithelium-Derived Factor; C039671:ciglitazone