INHIBITION OF GROWTH AND DNA SYNTHESIS OF CELLS FROM AN ALVEOLAR CELL CARCINOMA BY GLUCOCORTICOIDS

Abstract

Glucocorticoids have been reported to inhibit lung growth and to induce differentiated function in fetal lung in many species. We have used the A-549 cell line, derived from a human alveolar cell carcinoma, to study corticosteroid-induced growth inhibition We found that dexamethasone (DM) inhibits the growth of these cells and that this inhibition is concentration dependent, being identifiable at 10^-9M DM and near maximum at 4 × 10^-8M. Population doubling time of the cells was increased from 28.4 hours in control conditions to 66.5 hours in dexamethasone. DNA synthesis was also inhibited by DM with a concentration response similar to that seen with inhibition of cell growth. Several other steroids tested inhibited DNA synthesis, with their inhibiting potential corresponding to their known glucocorticoid potency (dexamethasone > cortisol > corticosterone > deoxycorticosterone). Testosterone and estradiol were not inhibitory. Cytosois from these cells bound ³H-dexamethasone with high affinity and limited capacity. Other glucocorticoids decrease ³H-DM binding in a pattern which correlates with their growth inhibiting activity and biologic activity. The corticosteroid induced growth inhibition in these cells is not cytolytic and may be characteristic of an anabolic pattern of growth arrest associated with induction of differentiated function.

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