The effects of suramin on human adrenocortical cells in vitro: suramin inhibits cortisol secretion and adrenocortical cell growth.
Suramin, a polycyclic and polyanionic drug, has been successfully used in the therapy of inoperable adrenocortical cancer. The present study was undertaken to investigate the effects of suramin on normal human adrenocortical cells in primary monolayer cultures. The proliferation and the basal, as well as the adrenocorticotropin (ACTH)-stimulated, cortisol secretion of these cells were studied. The data show that suramin decreases basal, as well as ACTH-stimulated, cortisol secretion in a dose-dependent manner (P less than .05 from 300 mumol/L upward). At a suramin concentration of 3 mmol/L, cortisol secretion was inhibited by 70% +/- 4% in ACTH-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was also inhibited by suramin at concentrations from 300 mumol/L upward, maximal suppression (71% +/- 6%, P less than .01) being observed at a concentration of 10 mmol/L. Both inhibition of cortisol secretion and inhibition of adrenocortical cell proliferation were not due to toxicity of the compound, as could be shown by restimulation of cortisol secretion in suramin-treated cells with ACTH. Our results indicate that suramin exerts an inhibitory influence on the cortisol secretion and on the proliferation of normal human adrenocortical cells. Suramin may not only be useful in the treatment of adrenocortical cancer, but may also have an ameliorative effect on other malignant conditions with augmented steroid hormone production, resistant to conventional forms of therapy.
Dorfinger
K
K
Department of General and Experimental Pathology, University of Vienna, Austria.
Vierhapper
H
H
Wilfing
A
A
Czernin
S
S
Niederle
B
B
Nowotny
P
P
Peterlik
M
M
Waldhäusl
W
W
Grubeck-Loebenstein
B
B
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013498:Suramin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D013498:Suramin; D000324:Adrenocorticotropic Hormone; D013936:Thymidine; D006854:Hydrocortisone