Griseofulvin increases steroid hormone levels in the supernatant of adrenocortical cells in vitro

Abstract

It has been shown that griseofulvin, which is an antifungal drug, inhibits growth of adrenocortical cancer cells in vitro. The inhibition of growth is caused by interactions with the microtubule apparatus. Interestingly, the microtubule apparatus is also involved in the regulation of steroidogenesis. Therefore we posed the question if griseofulvin also affects steroid hormone secretion. We have applied the NCI-H295R adrenocortical cancer cell line for the analysis of the effects of griseofulvin on adrenocortical steroid hormone secretion. Cells were incubated with or without griseofulvin at concentrations of 0.1µM, 1µM, 10µM, 40µM and 100µM for 24 hours. Concentrations of aldosterone, cortisol and dehydroepiandrostenedione (DHEA) were analyzed in the supernatants using Enzyme Linked Immunosorbent Assays (ELISAs). In addition, we measured concentrations of potassium levels to rule out that increased steroid hormone levels were a consequence of changed electrolyte concentrations. The incubation with griseofulvin leads to a dose dependent increase of Aldosterone-(approximately 2.3-fold), Cortisol-(approximately 1.3-fold) and DHEA-(approximately 4.3 fold) concentrations. The effects were, at least in part, independent from the concentration of potassium. Griseofulvin interfere with the microtubule apparatus and may disrupt regular trafficking of intracellular steroidal compounds. Apoptosis of adrenocortical cells may contribute to the release of steroid hormones. However, the exact mechanism how griseofulvin leads to increased concentrations of steroid hormones in the supernatant of adrenocortical cells is still unclear.