Morrissey Colm, Bektic Jasmin, Spengler Barbara, Galvin David, Christoffel Volker, Klocker Helmut, Fitzpatrick John M, Watson R William G
Department of Surgery, Mater Misericordiae University Hospital, Conway Institute of Biomolecular and Biomedical Research, Dublin Molecular Medicine Centre, University College Dublin, Dublin, Ireland.
J Urol. 2004 Dec;172(6 Pt 1):2426-33. doi: 10.1097/01.ju.0000143537.86596.66.
Phytoestrogens are nonsteroidal plant derived compounds with estrogenic activity that have been implicated in protecting against prostate cancer progression. We hypothesized that these compounds would alter cell number and increase the ability of antiandrogens to induce cell death in prostate cancer cells.
RWPE-1, LNCaP and PC-3 cells were treated with or without an extract of Belamcanda chinensis, 2 purified phytoestrogens derived from this extract (irigenin and tectorigenin) and the antiandrogen bicalutamide. We assessed the effect on cell number, proliferation and apoptosis.
Phytoestrogens (50 to 100 microM) and bicalutamide (10 to 50 microM) alone decreased the cell number in all 3 cell lines. Phytoestrogens (50 microM) combined with bicalutamide (10 microM) further decreased the number of RWPE-1 and PC-3 cells compared to these agents alone. Tectorigenin and irigenin inhibited the proliferation of RWPE-1, LNCaP and PC-3 cells, causing G1 arrest and the induction of p21WAF1 or p27 protein expression, whereas bicalutamide induced apoptosis in a dose dependent manner in all 3 cell lines. Phytoestrogens did not have antiandrogenic activity.
These in vitro studies demonstrate a role for tectorigenin and irigenin in regulating prostate cancer cell number by inhibiting proliferation through cell cycle regulation.
植物雌激素是一类具有雌激素活性的非甾体类植物衍生化合物,被认为对预防前列腺癌进展具有保护作用。我们推测这些化合物会改变细胞数量,并增强抗雄激素药物诱导前列腺癌细胞死亡的能力。
用射干提取物、从该提取物中纯化得到的2种植物雌激素(鸢尾苷元和鸢尾黄酮)以及抗雄激素比卡鲁胺处理RWPE-1、LNCaP和PC-3细胞,处理组和未处理组均进行实验。我们评估了这些处理对细胞数量、增殖和凋亡的影响。
单独使用植物雌激素(50至100微摩尔)和比卡鲁胺(10至50微摩尔)均能降低所有3种细胞系的细胞数量。与单独使用这些药物相比,植物雌激素(50微摩尔)与比卡鲁胺(10微摩尔)联合使用能进一步降低RWPE-1和PC-3细胞的数量。鸢尾黄酮和鸢尾苷元抑制RWPE-1、LNCaP和PC-3细胞的增殖,导致G1期阻滞并诱导p21WAF1或p27蛋白表达,而比卡鲁胺在所有3种细胞系中均以剂量依赖性方式诱导细胞凋亡。植物雌激素不具有抗雄激素活性。
这些体外研究表明,鸢尾黄酮和鸢尾苷元通过细胞周期调控抑制增殖,从而在调节前列腺癌细胞数量方面发挥作用。