Naiki-Ito Aya, Chewonarin Teera, Tang Mingxi, Pitchakarn Pornsiri, Kuno Toshiya, Ogawa Kumiko, Asamoto Makoto, Shirai Tomoyuki, Takahashi Satoru
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Prostate. 2015 Feb;75(2):151-60. doi: 10.1002/pros.22900. Epub 2014 Oct 4.
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.
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).
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.
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.
鞣花酸（EA）是石榴汁（PFJ）的一种成分，是一种植物来源的多酚，具有抗氧化特性。据报道，PFJ和EA可抑制包括前列腺癌在内的多种癌症。然而，它们在体内模型中对前列腺癌发生和发展的化学预防作用尚未确定。
使用前列腺腺癌转基因大鼠（TRAP）模型研究PFJ和EA对前列腺癌发生的调节作用。对3周龄雄性转基因大鼠用EA或PFJ处理10周。使用人前列腺癌细胞系LNCaP（雄激素依赖型）、PC-3和DU145（雄激素非依赖型）进行细胞生长、凋亡和蛋白质印迹的体外测定。
PFJ降低了外侧前列腺腺癌的发生率，在TRAP模型中，EA和PFJ均抑制前列腺癌发生的进展并通过激活caspase 3诱导凋亡。此外，EA处理显著降低了腹侧前列腺的脂质过氧化水平。EA能够抑制LNCaP的细胞增殖，而在PC-3和DU145中未观察到这种作用。与体内数据一致。EA通过增加Bax/Bcl-2比值和激活caspase 3诱导LNCaP凋亡。EA处理使细胞周期相关蛋白p21（WAF）、p27（Kip）、cdk2和细胞周期蛋白E增加，而细胞周期蛋白D1和cdk1减少。
结果表明，PFJ和EA是前列腺癌潜在的化学预防剂，EA可能是PFJ发挥这些抗癌作用的活性成分。
