Differentiation status modulates transcription factor NF-κB activity in unstimulated human hepatocellular carcinoma cell lines

We report herein a novel finding that under an unstimulated condition, a group of four human hepatocellular carcinoma (HCC) cell lines with varying degrees of differentiation, can spontaneously activate NF-κB. The propensity of activation coincided inversely with the differentiation status, with order being SK-Hep-1>J5>Hep3B>HepG2. Further studies indicate that this pattern of activation correlates excellently with the descending order of intracellular GSH/GSSG ratios as well as with the ascending order in the ability of these cells to generate hydrogen peroxide. Taken together, our data suggest that differentiation status may play a pivotal role in modulating intracellular thiol redox status and the extent of catalase expression, which may be crucial in the control of NF-κB activity in these HCC cells.