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

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.

SUBMITTER: Wang X

PROVIDER: S-EPMC8329194 | biostudies-literature |

REPOSITORIES: biostudies-literature

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White Button Mushroom (Agaricus bisporus) Interrupts Tissue AR-TMPRSS2 Expression and Attenuates Pro-inflammatory Cytokines in C57BL/6 Mice: Implication for COVID-19 Dietary Intervention.

Project description:Transmembrane protease serine 2 (TMPRSS2), an androgen-induced protease associated with prostate cancer, is one putative receptor for coronavirus entry into host cells, where triggering aggressive inflammatory cytokine storm and possibly death in COVID-19 patients. We previously reported that dietary white button mushroom (WBM) antagonized dihydrotestosterone (DHT)-induced androgen receptor (AR) activation and reduced myeloid-derived suppressor cells (MDSCs) in prostate cancer animal models and patients. The present study on C57BL/6 mice revealed that WBM is a unique food that A ) interrupts DHT induced AR-TMPRSS2 expression in putative COVID-19 targeted organs through its AR antagonistic activity and B ) attenuates serum pro-inflammatory cytokines which have been implicated in COVID-19 pathogenesis. We hereby propose WBM intake as a potentially low-cost, efficient, and safe dietary intervention to mitigate COVID-19.

| S-EPMC8010737 | biostudies-literature

Liver protective effects of white button mushroom (Agaricus Bisporus)

Project description:To study the mechanism of protective effect by White Button Mushroom (WBM) for Nonalcoholic Fatty Liver Disease (NAFLD) in ovariectomized mice (model for postmenopausal women). The ovariectomized mice were fed WBM diet for 3 month, sacrificed to harvest liver. 4 mice for control diet and 4 mice for WBM diet.

2012-03-01 | E-GEOD-31854 | biostudies-arrayexpress

Liver protective effects of white button mushroom (Agaricus Bisporus)

2012-03-01 | GSE31854 | GEO

White Button Mushroom (Agaricus bisporus) Disrupts Androgen Receptor Signaling in Human Prostate Cancer Cells (LNCaP)

Project description:Purpose: To evalute the antagonistic effects of White Button Mushroom/WBM extract on AR signaling in human prostate cance cells. Methods: LNCaP cells were treated with 1 nM DHT, with or without WBM extract (3 μL/mL), for 48h, in triplicates, and total RNA was isolated and sequenced. Results: We identified 155 up-regulated genes (Fold-change ≥ 2, p<0.05) versus 185 down-regulated genes (Fold-change ≤ 0.5, p<0.05). Conclusion: White Button Mushroom suppressed androgen respsonive genens and cell cycle division genes Collectively, these results suggest that WBM extract affects prostate cancer by interrupting AR-dependent cell cycle division and DNA replication.

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Management of Green Mold Disease in White Button Mushroom (<i>Agaricus bisporus</i>) and Its Yield Improvement.

Project description:Mycoparasites cause serious losses in profitable mushroom farms worldwide. The negative impact of green mold (Trichoderma harzianum) reduces cropping surface and damages basidiomes, limiting production and harvest quality. The goal of the current study was to evaluate new generation fungicides, to devise suitable management strategies against the green mold disease under prevailing agro-climatic conditions. Six non-systemic and five systemic fungitoxicants were evaluated for their efficacy against pathogen, T. harzianum, and host, Agaricus bisporus, under in vitro conditions. Among non-systemic fungicides, chlorothalonil and prochloraz manganese with mean mycelium inhibition of 76.87 and 93.40 percent, respectively, were highly inhibitory against the pathogen. The least inhibition percentage of 7.16 of A. bisporus was exhibited by chlorothalonil. Under in vivo conditions, use of captan 50 WP resulted in a maximum yield of button mushroom of 14.96 kg/qt. So far, systemic fungicides were concerned, carbendazim proved extremely inhibitory to the pathogen (89.22%), with least inhibitory effect on host mycelium (1.56%). However, application of non-systemic fungitoxicants further revealed that fungicide prochloraz manganese 50 WP at 0.1-0.2 percent or chlorothalonil 50 WP at 0.2 percent, exhibited maximum disease control of 89.06-96.30 percent. Moreover, the results of systemic fungitoxicants showed that carbendazim 50 WP or thiophanate methyl 70 WP at 0.1 percent reduced disease to 2.29-3.69 percent, hence exhibiting the disease control of 80.11-87.66 percent. Under in vivo conditions, fungicide myclobutanil at 0.1 percent concentration produced the maximum button mushroom production of 12.87 kg/q.

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Inactivation of AR/TMPRSS2-ERG/Wnt signaling networks attenuates the aggressive behavior of prostate cancer cells.

Project description:The development of prostate cancer and its progression to castrate-resistant prostate cancer (CRPC) after antiandrogen ablation therapy are driven by persistent biological activity of androgen receptor (AR) signaling. Moreover, studies have shown that more than 50% of human prostate cancers overexpress ERG (v-ets avian erythroblastosis virus E26 oncogene related gene) due to AR-regulated TMPRSS2-ERG fusion gene. However, the reported roles of TMPRSS2-ERG fusion in cancer progression are not clear. In this study, we investigated the signal transduction in the AR/TMPRSS2-ERG/Wnt signaling network for studying the aggressive behavior of prostate cancer cells and further assessed the effects of BR-DIM and CDF [natural agents-derived synthetic formulation and analogue of 3,3'-diindolylmethane (DIM) and curcumin, respectively, with improved bioavailability] on the regulation of AR/TMPRSS2-ERG/Wnt signaling. We found that activation of AR resulted in the induction of ERG expression through TMPRSS2-ERG fusion. Moreover, we found that ERG overexpression and nuclear translocation activated the activity of Wnt signaling. Furthermore, forced overexpression of ERG promoted invasive capacity of prostate cancer cells. More important, we found that BR-DIM and CDF inhibited the signal transduction in the AR/TMPRSS2-ERG/Wnt signaling network, leading to the inactivation of Wnt signaling consistent with inhibition of prostate cancer cell invasion. In addition, BR-DIM and CDF inhibited proliferation of prostate cancer cells and induced apoptotic cell death. On the basis of our findings, we conclude that because BR-DIM and CDF downregulate multiple signaling pathways including AR/TMPRSS2-ERG/Wnt signaling, these agents could be useful for designing novel strategies for the prevention and/or treatment of prostate cancer.

| S-EPMC3167947 | biostudies-literature

White button mushroom (Agaricus bisporus) disrupts androgen receptor signaling in human prostate cancer cells and patient-derived xenograft.

Project description:White button mushroom (WBM) (Agaricus bisporus) is a potential prostate cancer (PCa) chemo-preventative and therapeutic agent. Our clinical phase І 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.

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White Button Mushroom Extracts Modulate Hepatic Fibrosis Progression, Inflammation, and Oxidative Stress In Vitro and in LDLR-/- Mice.

Project description:Liver fibrosis can be caused by non-alcoholic steatohepatitis (NASH), among other conditions. We performed a study to analyze the effects of a nontoxic, water-soluble extract of the edible mushroom Agaricus bisporus (AB) as a potential inhibitor of fibrosis progression in vitro using human hepatic stellate cell (LX2) cultures and in vivo in LDLR-/- mice. Treatment of LX2 cells with the AB extract reduced the levels of fibrotic and oxidative-related markers and increased the levels of GATA4 expression. In LDLR-/- mice with high-fat diet (HFD)-induced liver fibrosis and inflammation, the progression of fibrosis, oxidative stress, inflammation, and apoptosis were prevented by AB extract treatment. Moreover, in the mouse model, AB extract could exert an antiatherogenic effect. These data suggest that AB mushroom extract seems to exert protective effects by alleviating inflammation and oxidative stress during the progression of liver fibrosis, possibly due to a decrease in Toll-like receptor 4 (TLR4) expression and a reduction in Nod-like receptor protein 3 (NLRP3) inflammasome activation. In addition, we observed a potential atheroprotective effect in our mouse model.

| S-EPMC8392037 | biostudies-literature

ATF5 Attenuates the Secretion of Pro-Inflammatory Cytokines in Activated Microglia.

Project description:The highly dynamic changes in microglia necessary to achieve a rapid neuroinflammatory response require a supply of energy from mitochondrial respiration, which leads to the accumulation of unfolded mitochondrial proteins. We previously reported that microglial activation is correlated with the mitochondrial unfolded protein response (UPRmt) in a kaolin-induced hydrocephalus model, but we still do not know the extent to which these changes in microglia are involved in cytokine release. Here, we investigated the activation of BV-2 cells and found that treatment with lipopolysaccharide (LPS) for 48 h increased the secretion of pro-inflammatory cytokines. This increase was accompanied by a concurrent decrease in oxygen consumption rate (OCR) and mitochondrial membrane potential (MMP), in association with the up-regulation of the UPRmt. Inhibition of the UPRmt by knockdown of ATF5, a key upstream regulator of the UPRmt, using small-interfering RNA against ATF5 (siATF5) not only increased production of the pro-inflammatory cytokines, interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α), but also decreased MMP. Our results suggest that ATF5-dependent induction of the UPRmt in microglia acts as a protective mechanism during neuroinflammation and may be a potential therapeutic target for reducing neuroinflammation.

| S-EPMC9961550 | biostudies-literature

Protective effects of white button mushroom (Agaricus bisporus) against hepatic steatosis in ovariectomized mice as a model of postmenopausal women.

Project description:Nonalcoholic fatty liver disease (NAFLD) includes various hepatic pathologies ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Estrogen provides a protective effect on the development of NAFLD in women. Therefore, postmenopausal women have a higher risk of developing NAFLD. Hepatic steatosis is an early stage of fatty liver disease. Steatosis can develop to the aggressive stages (nonalcoholic steatohepatitis, fibrosis and cirrhosis). Currently, there is no specific drug to prevent/treat these liver diseases. In this study, we found that white button mushroom (WBM), Agaricus Bisporus, has protective effects against liver steatosis in ovariectomized (OVX) mice (a model of postmenopausal women). OVX mice were fed a high fat diet supplemented with WBM powder. We found that dietary WBM intake significantly lowered liver weight and hepatic injury markers in OVX mice. Pathological examination of liver tissue showed less fat accumulation in the livers of mice on WBM diet; moreover, these animals had improved glucose clearance ability. Microarray analysis revealed that genes related to the fatty acid biosynthesis pathway, particularly the genes for fatty acid synthetase (Fas) and fatty acid elongase 6 (Elovl6), were down-regulated in the liver of mushroom-fed mice. In vitro mechanistic studies using the HepG2 cell line showed that down-regulation of the expression of FAS and ELOVL6 by WBM extract was through inhibition of Liver X receptor (LXR) signaling and its downstream transcriptional factor SREBP1c. These results suggest that WBM is protective against hepatic steatosis and NAFLD in OVX mice as a model for postmenopausal women.

| S-EPMC3201963 | biostudies-literature

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