Methylated urolithin A, the modified ellagitannin-derived metabolite, suppresses cell viability of DU145 human prostate cancer cells via targeting miR-21

Zhou, Benhong; Wang, Jing; Zheng, Guohua; Qiu, Zhenpeng

doi:10.1016/j.fct.2016.10.005

Cited by 50 publications

(43 citation statements)

References 44 publications

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“…The supplementation of ellagitanninʼs rich products was shown to decrease IGF-1/IGFBP-3 ratio in vivo, limiting the amount of IGF-1 available for interaction with its receptor and subsequent PI3K activation [8,34]. However, another study also reported decrease of Ser473 Akt phosphorylation in DU-145 cells by methylated uroA [35]. In our opinion, the differences in PTEN and AR status between LNCaP and DU-145 cell lines as well as TRAMP model are the main cause of observed discrepancy.…”

Section: Resultsmentioning

confidence: 99%

The Activity of Urolithin A and M4 Valerolactone, Colonic Microbiota Metabolites of Polyphenols, in a Prostate Cancer In Vitro Model

et al. 2018

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The gut microbiota-derived metabolites of ellagitannins and green tea catechins, urolithin A (uroA) and 5-(3′,4′,5′-trihydroxyphenyl)-γ-valerolactone (M4), respectively, are among the main compounds absorbed into human system after ingestion of these polyphenols. The aim of this study was to establish the effects of M4, uroA, and their combinations on LNCaP cells, an androgen dependent prostate cancer in vitro model.. The LNCaP cells were incubated with increasing concentrations of tested metabolites. The cell proliferation was determined by measurement of DNA-bisbenzimide H 33 258 complexes fluorescence. The isobolographic analysis was used to establish the type of interaction between metabolites. The apoptosis, androgen receptor (AR) localization, and phosphorylation of Akt kinase were measured by flow cytometry. Prostate-specific antigen (PSA) secretion was determined by ELISA. M4 showed modest antiproliferative activity in LNCaP cells (IC50 = 117 µM; CI: 81 – 154). UroA decreased proliferation (IC50 = 32.7 µM; CI: 24.3 – 41.1) and induced apoptosis of LNCaP cells. The mixture of M4 with uroA had synergistic antiproliferative effect. Moreover, M4 potentiated inhibition of PSA secretion and enhanced retention of AR in cytoplasm caused by uroA. Interestingly, uroA increased levels of pSer473 Akt in LNCaP cells. These results show that colonic metabolites may contribute to chemoprevention of prostate cancer by varied polyphenol-rich diet or composite polyphenol preparations.

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Section: Resultsmentioning

confidence: 99%

The Activity of Urolithin A and M4 Valerolactone, Colonic Microbiota Metabolites of Polyphenols, in a Prostate Cancer In Vitro Model

et al. 2018

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“…The BRB, for example, when evaluated by a non‐targeted metabolomic analysis showed over 4000 different UPLC peaks. [ 50 ] We chose to study BRBs based upon the anti‐cancer bioactivity of relevant phytochemicals in vitro [ 12–14,17,41,54,55 ] and accumulating studies of cancer preventive activity in rodent models. [ 16,19,40,47,56,57 ] Notably, due to the modest exposure of most populations to BRBs and the lack of specificity of berry intake on food frequency questionnaires, it is unlikely that epidemiological studies will provide insightful data regarding BRBs and cancer risk or other health outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…This cohort was chosen based upon preclinical research supporting potential bioactivity of berry polyphenols as inhibitors of prostate carcinogenesis. [ 14–17,28,29,40,41 ] Men had biopsy‐proven and clinically localized adenocarcinoma of the prostate based upon exam and imaging and selected a radical prostatectomy for curative treatment of their PCa. [ 42 ] Detailed eligibility criteria has been reported elsewhere.…”

Section: Methodsmentioning

confidence: 99%

Dose‐Dependent Increases in Ellagitannin Metabolites as Biomarkers of Intake in Humans Consuming Standardized Black Raspberry Food Products Designed for Clinical Trials

Roberts

Grainger

Thomas‐Ahner

et al. 2020

Molecular Nutrition Food Res

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Scope: Black raspberry (BRB) phytochemicals demonstrate anti-carcinogenic properties in experimental models, including prostate cancer. Two BRB foods, a confection and nectar, providing a consistent and reproducible product for human clinical studies are designed and characterized. Methods and results: Men with clinically localized prostate cancer are sequentially enrolled to a control group or one of four intervention groups (confection or nectar, 10 or 20 g dose; n = 8 per group) for 4 weeks prior to prostatectomy. Primary outcomes include: safety, adherence, and ellagitannin metabolism. Adherence to the intervention is >96%. No significant (≥grade II) toxicities are detected. Urinary urolithins (A, B, C, and D) and dimethyl ellagic acid (DMEA) quantified by Ultra high performance liquid chromatography tandem mass spectroscopy (UPLC/MS/MS) indicate a dose-dependent excretion yet heterogeneous patterns among men. Men in the BRB confection groups have greater urinary excretion of the microbial urinary metabolites urolithin A and DMEA, suggesting that this food matrix provides greater colonic microflora exposure. Conclusion: Fully characterized BRB confections and nectar are ideal for food-based large phase III human clinical studies. BRB products provide a bioavailable source of BRB phytochemicals, however large inter individual variation in polyphenol metabolism suggests that host genetics, microflora, and other factors are critical to understanding bioactivity and metabolism.

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“…miR-21, which is considered to be a proto-oncogene, is frequently reported as overexpressed in various cancer types and has been implicated in tumorigenesis (5,6). In addition, miR-21 has been reported to serve an important role in several signaling pathways, including Wnt/β-catenin and phosphatase and tensin homolog deletion on chromosome 10 (PTEN)/phosphatidylinositol 3-kinase (PI3K)/Akt (7,8). Furthermore, miR-21 may negatively regulate multiple target genes, including programmed cell death protein 4 (PDCD-4), tissue inhibitor of metalloproteinases-3, integrin subunit β 4 and PTEN (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of miR‑21 promotes cell apoptosis in oral squamous cell carcinoma by upregulating PTEN

et al. 2018

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MicroRNA‑21 (miR‑21) has been identified as an oncogene and confirmed to serve an important role in carcinogenesis in various types of cancer. However, the effect and mechanism of miR‑21 in oral squamous cell carcinoma (OSCC) has not been fully elucidated. In the present study, miR‑21 inhibitor and empty vector were transfected into OSCC cells, and non‑transfected cells were used as a blank control. The results indicated that when compared with the control and scramble groups, miR‑21 inhibitor suppressed the expression of miR‑21. Conversely, phosphatase and tensin homolog deletion on chromosome 10 (PTEN) was markedly upregulated, and a dual luciferase reporter assay revealed PTEN to be a target gene of miR‑21. Furthermore, miR‑21 inhibitor decreased the proliferation and invasion and enhanced the apoptosis of OSCC cells. There was no significant difference in cell proliferation, invasion and apoptosis between the control and scramble groups. The present data suggested that there may be a regulatory loop between miR‑21 and PTEN, and that miR‑21 inhibition affected the proliferative, invasive and apoptotic abilities of OSCC cells. These findings indicate that miR‑21 may be a possible novel target in the treatment of OSCC.

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Methylated urolithin A, the modified ellagitannin-derived metabolite, suppresses cell viability of DU145 human prostate cancer cells via targeting miR-21

Cited by 50 publications

References 44 publications

The Activity of Urolithin A and M4 Valerolactone, Colonic Microbiota Metabolites of Polyphenols, in a Prostate Cancer In Vitro Model

The Activity of Urolithin A and M4 Valerolactone, Colonic Microbiota Metabolites of Polyphenols, in a Prostate Cancer In Vitro Model

Dose‐Dependent Increases in Ellagitannin Metabolites as Biomarkers of Intake in Humans Consuming Standardized Black Raspberry Food Products Designed for Clinical Trials

Inhibition of miR‑21 promotes cell apoptosis in oral squamous cell carcinoma by upregulating PTEN

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