Growth inhibition by glucocorticoids in RPMI 3460 melanoma cells.
We have shown previously that dexamethasone inhibits the growth of RPMI 3460 melanoma cells and that cytosols of these cells contain a dexamethasone-binding macromolecule which has properties expected for a glucocorticoid receptor. In this paper, we show that two other glucocorticoids, triamcinolone acetonide and hydrocortisone, also cause growth inhibition in RPMI 3460 cells and that progesterone can block this response. The biological effect of these steroids correlates well with their previously reported ability to bind receptor, a result consistent with the concept that the glucocorticoid-induced growth inhibition is a receptor-mediated event. We have also investigated the nature of the growth response and shown that glucocorticoids inhibit growth in these melanoma cells by increasing the population-doubling time rather than by cytolytic effects. Moreover, a limited exposure to dexamethasone fails to trigger the growth inhibition, suggesting that the continued presence of steroid is necessary for growth inhibition to occur. Since serum-free medium and medium conditioned by exposure to cells do not affect the glucocorticoid-induced growth inhibition, we have obtained no evidence that either the interaction of glucocorticoids with serum factors or cell-induced changes in medium components are involved in the response. In addition to the effect on growth, we have also described morphological alterations which occur in the presence of dexamethasone.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003470:Culture Media; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006131:Growth Inhibitors; D006133:Growth Substances / Q000097:blood; D008545:Melanoma / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000473:pathology; D011374:Progesterone / Q000494:pharmacology
D003470:Culture Media; D006131:Growth Inhibitors; D006133:Growth Substances; D011374:Progesterone; D003907:Dexamethasone