Effect of caffeic acid phenethyl ester on proliferation and apoptosis of hepatic stellate cells in vitro.

Abstract

To investigate the role of nuclear factor-kappaB (NF-kappaB) inhibitor caffeic acid phenethy1 ester (CAPE) in the proliferation, collagen synthesis and apoptosis of hepatic stellate cells (HSCs) of rats. The HSCs from rats were isolated and cultured in Dulbecco's Modified Eagle's Medium (DMEM) and treated with CAPE. The proliferation and collagen synthesis of HSCs were determined by (3)H-TdR and (3)H-proline incorporation respectively, and the expression of type I, III procollagen genes was further explored by in situ hybridization. Apoptosis cell indices (AIs) were examined using terminal deoxynucleotidyl transferase- mediated DIG-dUTP nick end labeling (TUNEL). In activated HSC in culture, CAPE significantly inhibited (3)H-TdR and (3)H-proline incorporation by HSCs at concentrations of 5 micromol/L and 10 micromol/L respectively. CAPE also reduced the type I procollagen gene expression (P<0.05) at higher concentration. Apoptosis of HSC was induced by CAPE and the AIs were time-and dose-dependently increased from 2.82+/-0.73 % to 7.66+/-1.25 % at 12 h (P<0.01) and from 3.15+/-0.88 % to 10.61+/-2.88 % at 24 h (P<0.01). CAPE inhibits proliferation and collagen synthesis of HSC at lower concentration and induces HSC apoptosis at higher concentration.