|
KMID : 0043320200430040433
|
|
Archives of Pharmacal Research
2020 Volume.43 No. 4 p.433 ~ p.448
|
|
|
Transcriptional suppression of androgen receptor by 18β-glycyrrhetinic acid in LNCaP human prostate cancer cells
|
|
Sun You
Jiang Min-Gyue
Park Pil-Hoon
Song Kyung
|
|
|
Abstract
|
|
|
|
Androgen receptor (AR) plays a pivotal role as a target for amplification/mutation in pathogenesis and tumor progression in prostate, and thus, controlling AR activity or expression might be a feasible therapeutic approach for the treatment of prostate cancer. Here, we report the novel mechanisms by which 18β-glycyrrhetinic acid (GA) targets AR to stimulate cell death in both hormone-responsive and -refractory prostate cancer cells. We found that miR-488, a tumor suppressive microRNA, was markedly induced by GA treatment, resulting in the down-regulation of AR expression and inhibition of cellular responses mediated by androgens. Moreover, GA not only suppressed the expression of androgen target genes (TMPRSS2, PSA, and NKX3.1), but also enhanced the suppressive effect of anti-androgens (bicalutamide and flutamide) on LNCaP cell growth. Our data further provides evidence that down-regulation of AR expression by GA may occur through transcriptional suppression at AR promoter region between ??1014 and ??829. Ectopic expression of SFR and E2F3α reversed the inhibitory effect of GA on AR promoter activity as well as protein expression, suggesting that GA may target transcription factors SRF and E2F3α to regulate AR expression. Taken together, our study provides new insights on AR regulation and GA as a potential therapeutic candidate for human prostate cancer.
|
|
|
KEYWORD
|
|
|
Transcriptional suppression, Androgen receptor, 18β-glycyrrhetinic acid, miR-488, SRF, E2F3
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
  
|
|