Suramin and the human adrenocortex: results of experimental and clinical studies.
Suramin, a sulfonated drug, has been used successfully in the treatment of inoperable adrenocortical cancer. This study was undertaken to investigate the effects of suramin on the basal and the adrenocorticotropin-stimulated cortisol and pregnenolone secretion and on the proliferation of primary monolayer cultures of normal human adrenocortical cells. Suramin decreases basal and adrenocorticotropin-stimulated cortisol secretion in a dose-dependent manner (p less than 0.05 from 0.3 mmol/L upward). At a suramin concentration of 3 mmol/L cortisol, secretion was inhibited by 70% +/- 4% in adrenocorticotropin-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was inhibited by suramin at concentrations from 0.3 mmol/L upward, maximal suppression (71% +/- 6%; p less than 0.05) being observed at a concentration of 10 mmol/L. Neither down-regulation of cortisol secretion nor inhibition of adrenocortical cell proliferation was caused by toxicity of the compound, as could be shown by adrenocorticotropin-restimulating cortisol secretion in suramin-treated cells. The results indicate that suramin exerts an inhibitory influence on the cortisol secretion and the proliferation of normal human adrenocortical cells and may be useful in treating adrenocortical cancer.
Dorfinger
K
K
Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
Niederle
B
B
Vierhapper
H
H
Astrid
W
W
Czernin
S
S
Nowotny
P
P
Waldhäusl
W
W
Grubeck-Loebenstein
B
B
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D010865:Pilot Projects; D011284:Pregnenolone / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology*
D013498:Suramin; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone