Huaier Extract Inhibits Prostate Cancer Growth via Targeting AR/AR-V7 Pathway

• DOI: 10.3389/fonc.2021.615568
• Publication Date: 2021-02-23T05:26:12Z
• Authors: Zhengfang Liu; Cheng Liu; Keqiang Yan; Jikai Liu; Zhiqing Fang; Yidong Fan
• Keywords: Enzalutamide

The androgen receptor (AR) plays a pivotal role in prostatic carcinogenesis, and it also affects the transition from hormone sensitive prostate cancer (HSPC) to castration-resistant (CRPC). Particularly, persistent activation of appearance splicing variant 7 (AR-V7), could partly explain failure deprivation therapy (ADT). In present study, we reported that huaier extract, derived officinal fungi, has potent antiproliferative effects both HSPC CRPC cells. Mechanistically, extract downregulated full length AR (AR-FL) AR-V7 mRNA levels via targeting SET MYND domain-containing protein 3 (SMYD3) signaling pathway. Huaier enhanced proteasome-mediated degradation AR-FL by downregulating proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14). Furthermore, inhibited AR-FL/AR-V7 transcriptional activity their nuclear translocation. More importantly, our data demonstrated re-sensitize enzalutamide-resistant cells enzalutamide treatment vitro vivo models. Our work revealed be effective for either as monotherapy or combination with enzalutamide.