Huaier Extract Inhibits Prostate Cancer Growth via Targeting AR/AR-V7 Pathway
Pulmonary and Respiratory Medicine
0301 basic medicine
Ubiquitin-Proteasome Proteolytic Pathway
Cell biology
Carcinogenesis
androgen receptor splicing variant 7 (AR-V7)
Cancer research
Androgen deprivation therapy
03 medical and health sciences
Advancements in Prostate Cancer Research
0302 clinical medicine
Biochemistry, Genetics and Molecular Biology
Health Sciences
Enzalutamide
full length androgen receptor (AR-FL)
Molecular Biology
Biology
Internal medicine
RC254-282
Cancer
Chemotherapy-Induced Peripheral Neuropathy in Cancer Treatment
Prostate cancer
enzalutamide
Proteasome
Prostate Cancer
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Life Sciences
prostate cancer
3. Good health
Androgen receptor
Chemistry
Oncology
Androgen Receptor
Medicine
huaier extract
DOI:
10.3389/fonc.2021.615568
Publication Date:
2021-02-23T05:26:12Z
AUTHORS (6)
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.
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