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

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.

Efficacy and Safety of Huaier Granule as an Adjuvant Therapy for Cancer: An Overview of Systematic Reviews and Meta-Analyses

“…Huaier granule has broad-spectrum anticancer effects reflected in cancer types and enhancing efficacy of anticancer therapies. Except for above cancer types, many experimental studies have also shown its anticancer effect in other solid tumors including lung cancer, 22 cervical cancer, 23 renal cancer, 24 prostate cancer, 25 and cholangiocarcinoma 26 by various classic anticancer signaling pathways. 27 In addition, from this overview, we know that HG can enhance the efficacy of many anticancer therapies such as TACE, chemotherapy, radiotherapy, molecular targeted therapy, surgical resection, radiofrequency ablation to varying degrees.…”

Huaier Inhibits Gastric Cancer Growth and Hepatic Metastasis by Reducing Syntenin Expression and STAT3 Phosphorylation

“…The TCM Huaier ( Trametes robiniophila Murr.) has been used in the clinical treatment of various tumors, including gastric cancer [ 24 – 26 ]. At present, Huaier is clinically applied mainly as a water extract.…”

Therapeutic targets and signaling pathways of active components of QiLing decoction against castration-resistant prostate cancer based on network pharmacology

“…CRPC is a life-threatening PCa and studies have reported that CRPC may be ameliorated by the use of medicines, such as niclosamide ( Parikh et al, 2021 ) and huaier extract ( Liu et al, 2021 ). However, the active components and signaling pathways involved in treatment remain unknown.…”