title: Urolithin A causes p21 up-regulation in prostate cancer cells.
abstract: OBJECTIVE
  Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). The aim of this study was to determine gene expression changes in prostate cancer cells after incubation with UA.
  
  
  METHODS
  We performed a genomic analysis to study the effect of UA on LNCaP prostate cells. Cells were incubated with 40 µM UA for 24 h, and RNA was extracted and hybridized to Affymetrix Human Genome U219 array. Microarray results were analyzed using GeneSpring v13 software. Differentially expressed genes (p < 0.05, fold change > 2) were used to perform biological association networks. Cell cycle was analyzed by flow cytometry and apoptosis measured by the rhodamine method and by caspases 3 and 7 activation. Cell viability was determined by MTT assay.
  
  
  RESULTS
  We identified two nodes, FN-1 and CDKN1A, among the differentially expressed genes upon UA treatment. CDKN1A was validated, its mRNA and protein levels were significantly up-regulated, and the promoter activation measured by luciferase. Cell cycle analysis showed an increase in G1-phase, and we also observed an induction of apoptosis and caspases 3 and 7 activation upon UA treatment.
  
  
  CONCLUSIONS
  Our results indicate a potential role of UA as a chemopreventive agent for prostate cancer.
authors.affiliation: Nutrition and Food Science Department, University of Barcelona, 08028, Barcelona, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sánchez-González
authors.affiliation: Biochemistry and Molecular Biology Department, School of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain. cciudad@ub.edu.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Ciudad
authors.affiliation: Nutrition and Food Science Department, University of Barcelona, 08028, Barcelona, Spain.|CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Izquierdo-Pulido
authors.affiliation: Biochemistry and Molecular Biology Department, School of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain.
authors.forename: Véronique
authors.initials: V
authors.lastname: Noé
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D031324:Juglans / Q000737:chemistry; D008297:Male; D009754:Nuts / Q000737:chemistry; D059808:Polyphenols / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D003374:Coumarins; D050759:Cyclin-Dependent Kinase Inhibitor p21; C067625:FN1 protein, human; D005353:Fibronectins; D059808:Polyphenols; D012333:RNA, Messenger; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7
keywords: Ellagitannins cancer prevention; Urolithin A; Walnuts