ReferenceID 891
White button mushroom (Agaricus bisporus) disrupts androgen receptor signaling in human prostate cancer cells and patient-derived xenograft
J Nutr Biochem
White button mushroom (WBM) (Agaricus bisporus) is a potential prostate cancer (PCa) chemo-preventative and therapeutic agent. Our clinical phase I trial of WBM powder in patients with biochemically recurrent PCa indicat
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Record Fields
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- Reference Id
- 891
- Evidence Id
- 17481
- Core Evidence Id
- 17481
- Source Reference Id
- 1769
- Herb2 Reference Id
- HBREF002566
- Subject Paper Key
- HERB005147_33388344
- Pubmed Id
- 33388344
- Doi
- 10.1016/j.jnutbio.2020.108580
- Paper Title
- White button mushroom (Agaricus bisporus) disrupts androgen receptor signaling in human prostate cancer cells and patient-derived xenograft
- Paper Abstract
- White button mushroom (WBM) (Agaricus bisporus) is a potential prostate cancer (PCa) chemo-preventative and therapeutic agent. Our clinical phase I trial of WBM powder in patients with biochemically recurrent PCa indicated that WBM intake reduced the circulating levels of prostate-specific antigen (PSA). We hypothesized that WBM exerts its effects on PCa through the androgen receptor (AR) signaling axis. Therefore, we conducted a reverse translational study with androgen-dependent PCa cell lines (LNCaP and VCaP) and patient-derived-xenografts (PDX) from a prostate tumor (TM00298). In both LNCaP and VCaP cells, western blots and qRT-PCR assays indicated that WBM extract (6-30 mg/mL) suppressed DHT-induced PSA expression and cell proliferation in a dose-dependent manner. Immunofluorescence analysis of AR revealed that WBM extract interrupted the AR nuclear-cytoplasmic distribution. PSA promotor-luciferase assay suggested that WBM extract inhibited DHT-induced luciferase activity. RNA-Seq on WBM-treated LNCaP cells confirmed that WBM treatment suppressed the androgen response pathways and cell-cycle control pathways. Our PDX showed that oral intake of WBM extract (200 mg/kg/d) suppressed tumor growth and decreased PSA levels in both tumors and serum. In the present study, we also identified a conjugated linoleic acid isomer (CLA-9Z11E) as a strong AR antagonist by performing LanthaScreen TR-FRET AR Coactivator Interaction Assays. The inhibitory effect of CLA-9Z11E (IC50: 350 nM) was nearly two times stronger than the known AR antagonist, cyproterone acetate (IC50: 672 nM). The information gained from this study improves the overall understanding of how WBM may contribute to the prevention and treatment of PCa.
- Journal
- J Nutr Biochem
- Publish Year
- 2021
- Experiment Subject
- patient; androgen-dependent pca cell lines; lncap; vcap; vcap cells; wbm-treated lncap cells
- Experiment Type
- Clinical & Cell Experiment
- Phenotype Related
- Prostate Cancer; Prostate Tumor; Tumor; Tumors; Pca
- Paper Title Cn
- Paper Title En
- White button mushroom (Agaricus bisporus) disrupts androgen receptor signaling in human prostate cancer cells and patient-derived xenograft
- Bilingual Status
- semi_complete