Antagonism of androgen receptor signaling by aloe-emodin

Over the past decades, androgen receptor (AR) signaling has been a key driver of both primary and recurrent prostate cancer. In this work, aloe-emodin was identified as a novel AR antagonist, effectively inhibiting AR signaling. Firstly, aloe-emodin can inhibit LNCaP cell growth by promoting apoptosis. Then, the results of Western blot and quantitative real-time PCR further confirmed that aloe-emodin modulated AR protein levels by promoting AR proteasomal degradation, and also inhibited the transcription of the AR downstream target genes, including PSA, KLK2, and TMPRSS2. Furthermore, the result of immunofluorescence showed that aloe-emodin prevented the nuclear translocation of AR. Molecular docking and molecular dynamics simulation suggested that aloe-emodin combined with AR to form stable complexes, which might explain that aloe-emodin prevented the translocation of AR from the cytoplasm to the nucleus by affecting the ligand binding of AR. Therefore, aloe-emodin as a novel AR antagonist may play a crucial role in promoting cancer prevention or complementing pharmacological therapies in the treatment of prostate cancer. •Antagonism of androgen receptor (AR) signaling by aloe-emodin was confirmed herein.•Aloe-emodin inhibited LNCaP cell growth by promoting apoptosis.•Aloe-emodin bound to AR and prevented its nuclear translocation.•Aloe-emodin reduced AR protein level by promoting proteasomal degradation.•Aloe-emodin suppressed the transcription of the AR downstream target genes.