title: A double-blind, randomized, neoadjuvant study of the tissue effects of POMx pills in men with prostate cancer before radical prostatectomy.
abstract: Pomegranates slow prostate cancer xenograft growth and prolong prostate-specific antigen (PSA) doubling times in single-arm human studies. Pomegranates' effects on human prostate tissue are understudied. We hypothesized that orally administered pomegranate extract (POMx; Pom Wonderful) would lower tissue 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress biomarker. Seventy men were randomized to two tablets, POMx or placebo, daily up to four weeks before radical prostatectomy. Tissue was analyzed for intraprostatic urolithin A, a pomegranate metabolite, benign and malignant 8-OHdG, and cancer pS6 kinase, NF-κB, and Ki67. Primary endpoint was differences in 8-OHdG, and the study was powered to detect 35% reduction. POMx was associated with 16% lower benign tissue 8-OHdG (P = 0.095), which was not statistically significant. POMx was well tolerated with no treatment-related withdrawals. There were no differences in baseline clinicopathological features between arms. Urolithin A was detected in 21 of the 33 patients in the POMx group versus 12 of the 35 in the placebo group (P = 0.031). Cancer pS6 kinase, NF-κB, Ki67, and serum PSA changes were similar between arms. POMx before surgery results in pomegranate metabolite accumulation in prostate tissues. Our primary endpoint in this modest-sized short-term trial was negative. Future larger longer studies are needed to more definitively test whether POMx reduces prostate oxidative stress, as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology.
authors.affiliation: Duke University Medical Center, Box 2626, Durham, NC 27710. steve.freedland@duke.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
authors.forename: Michael
authors.initials: M
authors.lastname: Carducci
authors.forename: Nils
authors.initials: N
authors.lastname: Kroeger
authors.forename: Alan
authors.initials: A
authors.lastname: Partin
authors.forename: Jian-Yu
authors.initials: JY
authors.lastname: Rao
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Jin
authors.forename: Susan
authors.initials: S
authors.lastname: Kerkoutian
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Li
authors.forename: Patricia
authors.initials: P
authors.lastname: Creel
authors.forename: Kelly
authors.initials: K
authors.lastname: Mundy
authors.forename: Robin
authors.initials: R
authors.lastname: Gurganus
authors.forename: Helen
authors.initials: H
authors.lastname: Fedor
authors.forename: Serina A
authors.initials: SA
authors.lastname: King
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Heber
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Pantuck
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002853:Chromatography, Liquid; D003131:Combined Modality Therapy; D003374:Coumarins / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry; D004311:Double-Blind Method; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D029561:Lythraceae / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D020360:Neoadjuvant Therapy / Q000379:methods*; D018384:Oxidative Stress; D010936:Plant Extracts / Q000008:administration & dosage*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D003374:Coumarins; D019394:Ki-67 Antigen; D016328:NF-kappa B; D010936:Plant Extracts; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019893:Ribosomal Protein S6 Kinases; D017430:Prostate-Specific Antigen; D003849:Deoxyguanosine