An integrated in vitro/in silico approach to assess the anti-androgenic potency of isobavachin.

Isobavachin is a dietary flavanone with multiple biological activities. Our previous research has confirmed the estrogenicity of isobavachin, and this work aims to assess the anti-androgenic potency of isobavachin by an integrated in vitro and in silico approach. Isobavachin can limit the proliferation of prostate cancer cells by inducing a distinct G1 cell-cycle arrest. In addition, isobavachin also significantly represses the transcription of androgen receptor (AR)-downstream targets such as prostate specific antigen. Mechanistically, we demonstrated that isobavachin can disrupt the nuclear translocation of AR and promote its proteasomal degradation. The results of computer simulations showed that isobavachin can stably bind to AR, and the amino acid residue Gln711 may play a critical role in AR binding of both AR agonists and antagonists. In conclusion, this work has identified isobavachin as a novel AR antagonist.