title: Methylated urolithin A, the modified ellagitannin-derived metabolite, suppresses cell viability of DU145 human prostate cancer cells via targeting miR-21.
abstract: Urolithins are bioactive ellagic acid-derived metabolites produced by human colonic microflora. Although previous studies have demonstrated the cytotoxicity of urolithins, the effect of urolithins on miRNAs is still unclear. In this study, the suppressing effects of methylated urolithin A (mUA) on cell viability in human prostate cancer DU145 cells was investigated. mUA induced caspase-dependent cell apoptosis, mitochondrial depolarization and down-regulation of Bcl-2/Bax ratio. The results showed that upon exposure to mUA, miR-21 expression was decreased and the expression of PTEN and Pdcd4 protein was elevated. mUA could further suppress Akt phosphorylation and increase protein expression of FOXO3a, and the effects of mUA on Akt phosphorylation and protein expression of FOXO3a were blocked by PTEN silence. Moreover, mUA suppressed the Wnt/β-catenin-mediated transcriptional activation of MMP-7 and c-Myc, and this function of mUA on MMP-7 and c-Myc was attenuated by over-expression of miR-21. In conclusion, our data suggest that mUA can suppress cell viability in DU145 cells through modulating miR-21 and its downstream series-wound targets, including PTEN, Akt and Wnt/β-catenin signaling.
authors.affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China.
authors.forename: Benhong
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Chinese Medicine Resource and Compound Prescription (Ministry of Education), Hubei University of Chinese Medicine, Wuhan 430065, People's Republic of China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Zheng
authors.affiliation: College of Pharmacy, Hubei University of Chinese Medicine, No. 1, West Huangjiahu Road, Wuhan 430065, People's Republic of China. Electronic address: whuqq@hotmail.com.
authors.forename: Zhenpeng
authors.initials: Z
authors.lastname: Qiu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D003374:Coumarins / Q000494:pharmacology*; D000071316:Forkhead Box Protein O3 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D003374:Coumarins; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051821:Lymphoid Enhancer-Binding Factor 1; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051176:beta Catenin; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Akt; Methylated urolithin A; PTEN; miR-21; β-catenin