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Ellagic acid, a component of pomegranate fruit juice, suppresses androgen‐dependent prostate carcinogenesis via induction of apoptosis
Author(s) -
NaikiIto Aya,
Chewonarin Teera,
Tang Mingxi,
Pitchakarn Pornsiri,
Kuno Toshiya,
Ogawa Kumiko,
Asamoto Makoto,
Shirai Tomoyuki,
Takahashi Satoru
Publication year - 2015
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22900
Subject(s) - du145 , lncap , prostate cancer , cancer research , tramp , apoptosis , prostate , carcinogenesis , medicine , endocrinology , chemistry , cancer , biochemistry
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. Prostate 75:151–160, 2015 . © 2014 Wiley Periodicals, Inc.