Equol inhibits prostate cancer growth through degradation of androgen receptor by S‐phase kinase‐associated protein 2

Itsumi, Momoe; Shiota, Masaki; Takeuchi, Ario; Kashiwagi, Eiji; Inokuchi, Junichi; Tatsugami, Katsunori; Kajioka, Shunichi; Uchiumi, Takeshi; Naito, Seiji; Eto, Masatoshi; Yokomizo, Akira

doi:10.1111/cas.12948

Cited by 34 publications

(19 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The androgen‐activated transcription factor AR has been widely investigated. The AR features that contribute to the progression of prostate cancer consist of AR amplification, mutations, variants and alterations of coregulators, all of which lead to AR hyperactivity . In addition to what we described above, posttranscriptional regulation is also an efficient method for gene regulation.…”

Section: Discussionmentioning

confidence: 94%

RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

et al. 2020

View full text Add to dashboard Cite

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractThe androgen receptor (AR) pathway is critical for prostate cancer carcinogenesis and development; however, after 18-24 months of AR blocking therapy, patients invariably progress to castration-resistant prostate cancer (CRPC), which remains an urgent problem to be solved. Therefore, finding key molecules that interact with AR as novel strategies to treat prostate cancer and even CRPC is desperately needed. In the current study, we focused on the regulation of RNA-binding proteins (RBPs) associated with AR and determined that the mRNA and protein levels of AR were highly correlated with Musashi2 (MSI2) levels. MSI2 was upregulated in prostate cancer specimens and significantly correlated with advanced tumor grades. Downregulation of MSI2 in both androgen sensitive and insensitive prostate cancer cells inhibited tumor formation in vivo and decreased cell growth in vitro, which could be reversed by AR overexpression. Mechanistically, MSI2 directly bound to the 3′-untranslated region (UTR) of AR mRNA to increase its stability and, thus, enhanced its transcriptional activity. Our findings illustrate a previously unknown regulatory mechanism in prostate cancer cell proliferation regulated by the MSI2-AR axis and provide novel evidence towards a strategy against prostate cancer. K E Y W O R D Sandrogen receptor, mRNA stability, Musashi2, novel anti-androgen therapy, prostate cancer

show abstract

Section: Discussionmentioning

confidence: 94%

RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Also, S-equol inhibited the growth of PC3 xenograft tumors in BALB/c nude mice [15]. In another study led by Itsumi et al, equol was proved to be able to inhibit prostate tumor growth through degradating androgen receptor by S-phase kinase-associated protein 2 [16]. Equol exists as two distinct isomers, R-(+)equol and S-(−)equol, and the latter is the natural diastereoisomer produced by bacteria in the intestine of humans and rats.…”

Section: Resultsmentioning

confidence: 99%

High dietary fat intake lowers serum equol concentration and promotes prostate carcinogenesis in a transgenic mouse prostate model

Liu

Jiang

2019

Nutr Metab (Lond)

View full text Add to dashboard Cite

Background Consumption of diet high in soy products is suggested to contribute to lower prostate cancer incidence in Asian men. But little has been known about the influences of dietary patterns on gut microbiota and microbiota-mediated isoflavone metabolism. Here, we determined the influences of western pattern diet on prostate carcinogenesis, gut microbiota and microbiota-mediated equol metabolism using a transgenic adenocarcinoma of mouse prostate (TRAMP) model. Methods We mimicked the western pattern diet using a high fat diet (HFD). TRAMP mice were fed with either control diet (CD) or HFD. At the age of 24 weeks, mice were orally administered daidzein over a 4-day period, and then sacrificed. The serum daidzein and equol were analyzed by ultra high performance liquid chromatography. Fecal microbiome was analyzed with fecal 16S rRNA pyrosequencing, and prostate was dissected and performed with histopathology. Results HFD could promote prostate carcinogenesis in TRAMP mice ( p = 0.045). The daidzein showed no significant differences between CD and HFD groups, while equol was significantly decreased in HFD group ( p = 0.019). Fecal microbiotas differed between the two groups, 21 microbial phylotypes were increased and 11 phylotypes were decreased in abundance in HFD group, including decreased abundance of equol-producing bacterium Adlercreutzia (0.08% vs. 0.27%) . Conclusions HFD may promote prostate carcinogenesis through adversely affecting equol-producing bacterium. Further functional validations are required to ascertain the mechanism of those HFD-responsive bacteria in carcinogenesis.

show abstract

“…Adlercreutzia and Slackia are capable of metabolizing daidzein into equol [39]. Equol is an isoflavandiol manifesting phytoestrogenic activity with a potentially positive effect on human health, including hormonal and cardiovascular functions [40] and anticancer activity [41].…”

Section: Discussionmentioning

confidence: 99%

Human Gut Microbiome Response Induced by Fermented Dairy Product Intake in Healthy Volunteers

Volokh¹,

Klimenko

Berezhnaya³

et al. 2019

Nutrients

View full text Add to dashboard Cite

Accumulated data suggests that the gut microbiome can rapidly respond to changes in diet. Consumption of fermented dairy products (FDP) fortified with probiotic microbes may be associated with positive impact on human health. However, the extent and details of the possible impact of FDP consumption on gut community structure tends to vary across individuals. We used microbiome analysis to characterize changes in gut microbiota composition after 30 days of oral intake of a yoghurt fortified with Bifidobacterium animalis subsp. lactis BB-12. 16S rRNA gene sequencing was used to assess the gut microbial composition before and after FDP consumption in healthy adults (n = 150). Paired comparison of gut microbial content demonstrated an increase in presence of potentially beneficial bacteria, particularly, Bifidobacterium genus, as well as Adlercreutzia equolifaciens and Slackia isoflavoniconvertens. At a functional level, an increased capacity to metabolize lactose and synthesize amino acids was observed accompanied by a lowered potential for synthesis of lipopolysaccharides. Cluster analysis revealed that study volunteers segregated into two groups with post-intervention microbiota response that was dependent on the baseline microbial community structure.

show abstract

Equol inhibits prostate cancer growth through degradation of androgen receptor by S‐phase kinase‐associated protein 2

Cited by 34 publications

References 44 publications

RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

High dietary fat intake lowers serum equol concentration and promotes prostate carcinogenesis in a transgenic mouse prostate model

Human Gut Microbiome Response Induced by Fermented Dairy Product Intake in Healthy Volunteers

Contact Info

Product

Resources

About