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

Abstract

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.

Graphical Abstract

Keywords:

• Androgen receptor
• ergosterol
• LNCaP
• DU-145
• MTT bioassay
• molecular dynamics simulations

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors acknowledge to Dr. Elizabeth Langley-McCarron (National Cancer Institute, Mexico), for the donation of LNCaP and DU-145 cell lines. JSM and AVL gratefully acknowledge the computing time granted by LANCAD and CONACYT on the supercomputers Xiuhcoatl at CGSTIC CINVESTAV and Miztli at DGTIC UNAM. MMF thanks CONACYT for scholarship (46768). AVL thanks to BUAP LNS 201901025N and DGAPA IN 114815 grant projects. The authors thank to MSc. Aldo Rodríguez Guerrero and Héctor Oliver for technical assistence.