In vitro growth inhibition of human malignant melanoma cells by glucocorticoids.
The human malignant melanoma cell line, NEL, was found to contain glucocorticoid receptors. When the binding data were analyzed according to the method of Scatchard, results indicated a ligand binding capacity of 247 fmol/mg protein and a Kd of 1 X 10(-9) M. Additional studies show that the continuous incubation of NEL cells with triamcinolone acetonide (TA) for 72 hr results in a 30% inhibition in cell growth. To ascertain the mechanism by which glucocorticoids inhibit the growth of NEL cells, uptake and incorporation studies were carried out using various 3H precursors. Results indicate that, after 4 hr of TA treatment, a modest inhibition in [3H]thymidine uptake was observed, while stimulation of [3H]thymidine incorporation was noted at all steroid concentrations tested. However, cells incubated for 18 hr with TA (concentration, greater than or equal to 10(-8) M) showed a 30% decrease in the amount of [3H]thymidine incorporated into DNA. TA had no effect on [3H]leucine or [3H]glucose uptake after 4 hr of treatment but did inhibit [3H]glucose (42%) uptake after 18 hr of treatment. A slight stimulation (9%) in [3H]leucine incorporation was observed at this time point. When NEL cells were incubated with TA and the antiglucocorticoid, progesterone, the inhibition in [3H]thymidine incorporation was negated. These findings indicate that glucocorticoids exert some influence on the growth of human melanoma cells, and this effect is mediated through the glucocorticoid receptor.
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D011374:Progesterone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014222:Triamcinolone Acetonide / Q000494:pharmacology
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D011374:Progesterone; D014222:Triamcinolone Acetonide; D013936:Thymidine