Steroid metabolism in normal and transformed liver cells. Relation with glucocorticoid antagonism

The metabolism of the potent antagonist RU38486 has been studied in cultured liver cells and in two hepatoma cell lines. In the liver cells, this steroid undergoes a rapid degradation, whereas in hepatoma cells grown in similar conditions only a minor degradation occurs. Moreover the rate of degradation is much higher for the antagonist steroid than for the agonist steroid tested, dexamethasone. The high antiglucocorticoid potency and the relative instability of the RU38486 molecule are very important to define its different effects and its mechanism of action in liver and in liver derived tumor cells. RU38486 may represent a useful drug in cancerotherapy.