Boulbès Delphine, Soustelle Laurent, Costa Pierre, Haddoum Mohammed, Bali Jean-Pierre, Hollande Frédéric, Magous Richard
INSERM, U 03.37, Faculté de Médecine, Créteil, France.
BJU Int. 2006 Nov;98(5):1106-13. doi: 10.1111/j.1464-410X.2006.06483.x.
To investigate the effect of Pygeum africanum (PA) extract on the proliferation of cultured human prostatic myofibroblasts and fibroblasts; this extract is used for treating urinary disorders associated with benign prostatic hyperplasia (BPH).
Primary cultures of prostatic stromal cells were obtained from histologically confirmed human BPH by enzymatic digestion. Cell proliferation was measured by 5-bromo2'-deoxy-uridine (BrdU) incorporation assays, and cytotoxicity by luminescent quantification of adenylate kinase activity.
Cultured cells were labelled by an anti-vimentin antibody, and most of them by an alpha-smooth-muscle-actin antibody, revealing the presence of fibroblasts and myofibroblasts. BrdU incorporation tests showed that proliferation of cultured human stromal cells, stimulated by fetal calf serum, by basic fibroblast growth factor and by epidermal growth factor, was dose-dependently inhibited by PA extract (5-100 microg/mL). Except at 100 microg/mL, no acute cytotoxicity of the extract was detected after 24 h of culture. Similarly, the extract dose-dependently inhibited the proliferation of Madin-Darby canine kidney epithelial cells, but to a lesser extent; whatever the dose of extract, no acute toxicity was evident on this cell line.
PA extract inhibits the proliferation of cultured human prostatic myofibroblasts and fibroblasts. We propose that cultured human prostatic cells offer a reliable model for preclinical screening of therapeutic agents, and to study the mechanisms underlying the inhibition of proliferation.
研究非洲臀果木提取物对培养的人前列腺肌成纤维细胞和成纤维细胞增殖的影响;该提取物用于治疗与良性前列腺增生(BPH)相关的泌尿系统疾病。
通过酶消化从组织学确诊的人BPH中获得前列腺基质细胞的原代培养物。通过5-溴-2'-脱氧尿苷(BrdU)掺入试验测量细胞增殖,并通过腺苷酸激酶活性的发光定量测量细胞毒性。
培养的细胞用抗波形蛋白抗体标记,大多数细胞用α-平滑肌肌动蛋白抗体标记,表明存在成纤维细胞和肌成纤维细胞。BrdU掺入试验表明,由胎牛血清、碱性成纤维细胞生长因子和表皮生长因子刺激的培养人基质细胞的增殖被非洲臀果木提取物(5-100μg/mL)剂量依赖性抑制。除100μg/mL外,培养24小时后未检测到提取物的急性细胞毒性。同样,该提取物剂量依赖性抑制Madin-Darby犬肾上皮细胞的增殖,但程度较小;无论提取物剂量如何,该细胞系均未出现明显的急性毒性。
非洲臀果木提取物抑制培养的人前列腺肌成纤维细胞和成纤维细胞的增殖。我们认为,培养的人前列腺细胞为治疗药物的临床前筛选以及研究增殖抑制的潜在机制提供了一个可靠的模型。