title: Ellagic acid, a component of pomegranate fruit juice, suppresses androgen-dependent prostate carcinogenesis via induction of apoptosis.
abstract: BACKGROUND
  Ellagic acid (EA), a component of pomegranate fruit juice (PFJ), is a plant-derived polyphenol and has antioxidant properties. PFJ and EA have been reported to suppress various cancers, including prostate cancer. However, their chemopreventive effects on development and progression of prostate cancer using in vivo models have not been established yet.
  
  
  METHODS
  The transgenic rat for adenocarcinoma of prostate (TRAP) model was used to investigate the modulating effects of PFJ and EA on prostate carcinogenesis. Three-week-old male transgenic rats were treated with EA or PFJ for 10 weeks. In vitro assays for cell growth, apoptosis, and Western blot were performed using the human prostate cancer cell lines, LNCaP (androgen-dependent), PC-3 and DU145 (androgen-independent).
  
  
  RESULTS
  PFJ decreased the incidence of adenocarcinoma in lateral prostate, and both EA and PFJ suppressed the progression of prostate carcinogenesis and induced apoptosis by caspase 3 activation in the TRAP model. In addition, the level of lipid peroxidation in ventral prostate was significantly decreased by EA treatment. EA was able to inhibit cell proliferation of LNCaP, whereas this effect was not observed in PC-3 and DU145. As with the in vivo data, EA induced apoptosis in LNCaP by increasing Bax/Bcl-2 ratio and caspase 3 activation. Cell-cycle related proteins, p21(WAF) , p27(Kip) , cdk2, and cyclin E, were increased while cyclin D1 and cdk1 were decreased by EA treatment.
  
  
  CONCLUSIONS
  The results indicate that PFJ and EA are potential chemopreventive agents for prostate cancer, and EA may be the active component of PFJ that exerts these anti-cancer effects.
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Naiki-Ito
authors.forename: Teera
authors.initials: T
authors.lastname: Chewonarin
authors.forename: Mingxi
authors.initials: M
authors.lastname: Tang
authors.forename: Pornsiri
authors.initials: P
authors.lastname: Pitchakarn
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kuno
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Asamoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000726:Androgen Antagonists / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000728:Androgens / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001628:Beverages; D063646:Carcinogenesis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004610:Ellagic Acid / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D005638:Fruit; D006801:Humans; D029561:Lythraceae; D008297:Male; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D010936:Plant Extracts; D004610:Ellagic Acid
keywords: apoptosis; chemoprevention; ellagic acid; pomegranate; prostate cancer