Inhibition of growth by the antihormone RU486 in different hepatoma cell lines.

The synthetic steroid RU486 (17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha-(1-propynyl)-estra-4,9-dien-3-one), which has been shown to display antiprogestin and antiglucocorticoid properties in different systems, exerts antiglucocorticoid effects and inhibits the cell growth in a concentration-dependent manner on Reuber rat hepatoma cell variants. This effect can be observed on glucocorticoid-sensitive cells, containing glucocorticoid receptors, and on glucocorticoid-resistant cells displaying a very low level of dexamethasone binding. Metabolization of RU486 occurs in different glucocorticoid-resistant hepatoma variants; these cells are less sensitive to the growth inhibitory effect of the antihormone than the steroid-sensitive cells which do not metabolize RU486. Thus, metabolization of RU486 must also be taken into account for the efficacy of this antagonist on cell growth.