1. Academic Validation
  2. Huaier Extract Inhibits Prostate Cancer Growth via Targeting AR/AR-V7 Pathway

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

  • Front Oncol. 2021 Feb 23;11:615568. doi: 10.3389/fonc.2021.615568.
Zhengfang Liu 1 Cheng Liu 2 Keqiang Yan 1 Jikai Liu 1 Zhiqing Fang 1 3 Yidong Fan 1
Affiliations

Affiliations

  • 1 Department of Urology, Qilu Hospital of Shandong University, Ji'nan, China.
  • 2 Department of Urology, Peking University Third Hospital, Beijing, China.
  • 3 Department of Medicine, Center for Molecular Medicine (CMM) and Bioclinicum, Karolinska Institute and Karolinska University Hospital Solna, Solna, Sweden.
Abstract

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

Keywords

androgen receptor splicing variant 7 (AR-V7); enzalutamide; full length androgen receptor (AR-FL); huaier extract; prostate cancer.

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