title: Occurrence of urolithins, gut microbiota ellagic acid metabolites and proliferation markers expression response in the human prostate gland upon consumption of walnuts and pomegranate juice.
abstract: Epidemiology supports the important role of nutrition in prostate cancer (PCa) prevention. Pomegranate juice (PJ) exerts protective effects against PCa, mainly attributed to PJ ellagitannins (ETs). Our aim was to assess whether ETs or their metabolites ellagic acid and urolithins reach the human prostate upon consumption of ET-rich foods and to evaluate the effect on the expression of three proliferation biomarkers. Sixty-three patients with BPH or PCa were divided into controls and consumers of walnuts (35 g walnuts/day) or pomegranate (200 mL PJ/day) for 3 days before surgery. Independently of the ETs source, the main metabolite detected was urolithin A glucuronide, (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide) (up to 2 ng/g) together with the traces of urolithin B glucuronide, (3-hydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide) and dimethyl ellagic acid. The small number of prostates containing metabolites was likely caused by clearance of the compounds during the fasting. This was corroborated in a parallel rat study and thus the presence of higher quantities of metabolites at earlier time points cannot be discarded. No apparent changes in the expression of CDKN1A, MKi-67 or c-Myc were found after consumption of the walnuts or PJ. Our results suggest that urolithin glucuronides and dimethyl ellagic acid may be the molecules responsible for the beneficial effects of PJ against PCa.
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Sarrías
authors.forename: Juan A
authors.initials: JA
authors.lastname: Giménez-Bastida
authors.forename: María T
authors.initials: MT
authors.lastname: García-Conesa
authors.forename: María B
authors.initials: MB
authors.lastname: Gómez-Sánchez
authors.forename: Noelia V
authors.initials: NV
authors.lastname: García-Talavera
authors.forename: Angel
authors.initials: A
authors.lastname: Gil-Izquierdo
authors.forename: Carmen
authors.initials: C
authors.lastname: Sánchez-Alvarez
authors.forename: Luis O
authors.initials: LO
authors.lastname: Fontana-Compiano
authors.forename: Juan P
authors.initials: JP
authors.lastname: Morga-Egea
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Pastor-Quirante
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez-Díaz
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Tomás-Barberán
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Espín
mesh_terms: D000368:Aged; D000818:Animals; D001628:Beverages / Q000032:analysis; D014408:Biomarkers, Tumor / Q000378:metabolism; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004610:Ellagic Acid / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D005638:Fruit / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D020719:Glucuronides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D006801:Humans; D047348:Hydrolyzable Tannins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D031324:Juglans / Q000737:chemistry; D029561:Lythraceae / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D011467:Prostate / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000601:surgery / Q000652:urine; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000517:prevention & control / Q000601:surgery / Q000652:urine; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C576587:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one glucuronide; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D003374:Coumarins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D020719:Glucuronides; D047348:Hydrolyzable Tannins; D047908:Intracellular Signaling Peptides and Proteins; C489427:MYC protein, human; C492406:NIFK protein, human; D009687:Nuclear Proteins; D010936:Plant Extracts; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D004610:Ellagic Acid