Ergosterol exerts a differential effect on AR-dependent LNCaP and AR-independent DU-145 cancer cells

Androgen-dependent LNCaP and androgen-independent DU-145 cells, were treated with different concentrations of ergosterol (15 µM and 25 µM) and its respective cell viability was measured by MTT bioassay. While ergosterol showed an antiproliferative effect on LNCaP, on DU-145 promoted cell proliferation. This differential effect suggests that the effect of ergosterol might be related to its ability to act as an Androgen Receptor ligand. In silico Molecular Dynamics simulations were performed to analyze the interaction mechanism between androgen receptor and ergosterol, in comparison with natural ligands, 5α-dihydrotestosterone and testosterone. Our model suggests that the binding of androgen receptor with ergosterol is thermodinamically feasible, which is concordant with our experimental results.