White button mushroom interrupts tissue AR-mediated TMPRSS2 expression and attenuates pro-inflammatory cytokines in C57BL/6 mice

Xiaoqiang Wang,Desiree Ha,Shiuan Chen,Ryohei Yoshitake

doi:10.1038/s41538-021-00102-6

Abstract

White button mushroom (WBM) is a common edible mushroom consumed in the United States and many European and Asia-Pacific countries. We previously reported that dietary WBM antagonized dihydrotestosterone (DHT)-induced androgen receptor (AR) activation and reduced myeloid-derived suppressor cells (MDSCs) in prostate cancer animal models and patients. Transmembrane protease serine 2 (TMPRSS2), an androgen-induced protease in prostate cancer, has been implicated in influenza and coronavirus entry into the host cell, triggering host immune response. The present study on C57BL/6 mice revealed that WBM is a unique functional food that (A) interrupts AR-mediated TMPRSS2 expression in prostate, lungs, small intestine, and kidneys through its AR antagonistic activity and (B) attenuates serum pro-inflammatory cytokines and reduces MDSC counts through its immunoregulatory activity. These findings provide a scientific basis for translational studies toward clinical applications of WBM in diseases related to TMPRSS2 expression and immune dysregulation.

Highlights

White button mushroom (WBM) accounts for 90% of the total edible mushrooms consumed in the United States and many European and Asia-Pacific countries[1]
We recently reported that dietary WBM antagonized DHT-induced androgen receptor (AR) activation and prostate-specific antigen (PSA) expression in prostate cancer animal models and mouse prostate glands, without observable body weight loss, hepatotoxicity, and nephrotoxicity[3]
Levels of mRNA for AR and Transmembrane protease serine 2 (TMPRSS2) were highest in the prostate and ACE2 mRNA was highest in the small intestine (Fig. 1b)

Summary

Introduction

White button mushroom (WBM) accounts for 90% of the total edible mushrooms consumed in the United States and many European and Asia-Pacific countries[1]. We recently showed that chemicals in WBM antagonized dihydrotestosterone (DHT)-induced androgen receptor (AR) activation and PSA expression in prostate cancer cells and animal models[3]. Β-Glucans, the most abundant carbohydrate found in yeast and edible mushrooms, including WBM, are a well-established immune modulator that stimulates the proliferation of lymphocytes while reducing inflammatory factors[7]. Yeast and mushroom-derived β-glucans have been reported to suppress MDSCs8 in cancer models, enhancing immunity against tumor development[9]. Taken altogether, these findings suggest that chemicals in WBM exert both anti-androgenic and immunomodulatory effects

Methods

Results

Conclusion