Ellagic Acid, a Component of Pomegranate Fruit Juice, Suppresses Androgen-Dependent Prostate Carcinogenesis via Induction of Apoptosis
Ellagic Acid, a Component of Pomegranate Fruit Juice, Suppresses Androgen-Dependent Prostate Carcinogenesis via Induction of Apoptosis
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DOI：
10.1002/pros.22900
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发表时间：
2015-02-01
期刊：
影响因子：
2.8
通讯作者：
Takahashi, Satoru
中科院分区：
文献类型：
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作者：
Naiki-Ito, Aya;Chewonarin, Teera;Takahashi, Satoru
鞣花酸（EA）是石榴果汁（PFJ）的一种成分，是一种植物源性多酚，具有抗氧化特性。据报道，PFJ和EA可以抑制多种癌症，包括前列腺癌。然而，它们对前列腺癌发生和发展的化学预防作用尚未在体内模型中建立。方法采用转基因前列腺腺癌大鼠（TRAP）模型，研究PFJ和EA对前列腺癌发生的调节作用。3周龄雄性转基因大鼠分别用EA或PFJ治疗10周。使用人前列腺癌细胞系LNCaP（雄激素依赖性）、PC-3和DU145（雄激素非依赖性）进行细胞生长、凋亡和Western blot的体外检测。结果tspfj降低前列腺外侧腺癌的发生率，EA和PFJ在TRAP模型中均通过激活caspase 3抑制前列腺癌的进展并诱导细胞凋亡。此外，EA治疗可显著降低前列腺腹侧脂质过氧化水平。EA能够抑制LNCaP的细胞增殖，而PC-3和DU145则没有这种作用。与体内数据一样，EA通过增加Bax/Bcl-2比值和caspase 3激活来诱导LNCaP细胞凋亡。细胞周期相关蛋白p21（WAF）、p27（Kip）、cdk2和cyclin E升高，而cyclin D1和cdk1降低。结论PFJ和EA均为潜在的前列腺癌化学预防药物，EA可能是PFJ中发挥上述抗癌作用的活性成分。中华医学杂志（英文版），2015。(c) 2014 Wiley期刊公司
BACKGROUNDEllagic 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.METHODSThe 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).RESULTSPFJ 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.CONCLUSIONSThe 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. (c) 2014 Wiley Periodicals, Inc.