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 NH2-terminal kinases (JNKs) regulate c-FLIP expression in endothelial cells. The effect of PEDF on other cells remains unclear. Materials and 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. Conclusion: 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.
Original language | English |
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Pages (from-to) | 1173-1180 |
Number of pages | 8 |
Journal | Anticancer Research |
Volume | 31 |
Issue number | 4 |
State | Published - 04 2011 |
Keywords
- Apoptosis
- HCC
- Hepatocellular carcinoma
- PEDF
- PPARγ
- c-FLIP
- p38