Transcriptional suppression of androgen receptor by 18β-glycyrrhetinic acid in LNCaP human prostate cancer cells

다국어 초록 (Multilingual Abstract)

Androgen receptor (AR) plays a pivotal role as atarget for amplification/mutation in pathogenesis and tumorprogression in prostate, and thus, controlling AR activityor expression might be a feasible therapeutic approach forthe treatment of prostate cancer. Here, we report the novelmechanisms by which 18β-glycyrrhetinic acid (GA) targetsAR to stimulate cell death in both hormone-responsive and-refractory prostate cancer cells. We found that miR-488, atumor suppressive microRNA, was markedly induced by GAtreatment, resulting in the down-regulation of AR expressionand inhibition of cellular responses mediated by androgens.
Moreover, GA not only suppressed the expression of androgentarget genes (TMPRSS2, PSA, and NKX3.1), but alsoenhanced the suppressive effect of anti-androgens (bicalutamideand flutamide) on LNCaP cell growth. Our data furtherprovides evidence that down-regulation of AR expression byGA may occur through transcriptional suppression at AR promoter region between − 1014 and − 829. Ectopic expressionof SFR and E2F3α reversed the inhibitory effect of GAon AR promoter activity as well as protein expression, suggestingthat GA may target transcription factors SRF andE2F3α to regulate AR expression. Taken together, our studyprovides new insights on AR regulation and GA as a potentialtherapeutic candidate for human prostate cancer.

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