Gasmi Jihane, Sanderson J Thomas
Institut National de la Recherche Scientifique, Institut Armand-Frappier, Université du Québec, Laval, Québec H7 V1B7, Canada.
J Agric Food Chem. 2010 Dec 8;58(23):12149-56. doi: 10.1021/jf103306k. Epub 2010 Nov 10.
Prostate cancer is a commonly diagnosed cancer in men, and dietary chemoprevention by pomegranate (Punica granatum) extracts has shown noticeable benefits. In this study, we investigated the growth inhibitory, antiandrogenic, and pro-apoptotic effects of 13 pure compounds found in the pomegranate in androgen-dependent LNCaP human prostate cancer cells. Cells deprived of steroid hormones were exposed to increasing concentrations (1-100 μM) of pomegranate compounds in the presence of 0.1 nM dihydrotestosterone (DHT), and the inhibition of cell growth was measured by WST-1 colorimetric assay after a 4 day exposure. Four compounds, epigallocatechin gallate (EGCG), delphinidin chloride, kaempferol, and punicic acid, were found to inhibit DHT-stimulated cell growth at concentrations of 10 μM and above. These four pomegranate compounds inhibited DHT-stimulated androgen receptor nuclear accumulation and the expression of the androgen receptor-dependent genes prostate specific antigen and steroid 5α-reductase type 1 at concentrations ≥10 μM. We determined the possible contribution of apoptosis to the observed decrease in cell growth and found that three compounds, EGCG, kaempferol, and, in particular, punicic acid, induced DNA fragmentation after a 24 h treatment, at concentrations in the 10-100 μM range. Punicic acid, an important fatty acid in pomegranate seeds, was further found to induce intrinsic apoptosis via a caspase-dependent pathway. In conclusion, punicic acid, the main constituent of pomegranate seed (70-80%), exhibited potent growth inhibitory activities in androgen-dependent LNCaP cells, which appear to be mediated by both antiandrogenic and pro-apoptotic mechanisms.
前列腺癌是男性中常见的一种确诊癌症，而石榴（Punica granatum）提取物进行饮食化学预防已显示出显著益处。在本研究中，我们调查了石榴中发现的13种纯化合物对雄激素依赖性LNCaP人前列腺癌细胞的生长抑制、抗雄激素和促凋亡作用。将去除类固醇激素的细胞在存在0.1 nM二氢睾酮（DHT）的情况下暴露于浓度不断增加（1-100 μM）的石榴化合物中，在暴露4天后通过WST-1比色法测量细胞生长抑制情况。发现四种化合物，表没食子儿茶素没食子酸酯（EGCG）、氯化飞燕草素、山奈酚和石榴酸，在浓度为10 μM及以上时可抑制DHT刺激的细胞生长。这四种石榴化合物在浓度≥10 μM时可抑制DHT刺激的雄激素受体核积累以及雄激素受体依赖性基因前列腺特异性抗原和1型类固醇5α-还原酶的表达。我们确定了凋亡对观察到的细胞生长减少可能的贡献，发现三种化合物，EGCG、山奈酚，特别是石榴酸，在10-100 μM浓度范围内处理24小时后可诱导DNA片段化。石榴籽中的一种重要脂肪酸石榴酸，进一步被发现通过半胱天冬酶依赖性途径诱导内源性凋亡。总之，石榴籽的主要成分（70-80%）石榴酸在雄激素依赖性LNCaP细胞中表现出强大的生长抑制活性，这似乎是由抗雄激素和促凋亡机制介导的。
