Thelen Paul, Scharf Jens-Gerd, Burfeind Peter, Hemmerlein Bernhard, Wuttke Wolfgang, Spengler Barbara, Christoffel Volker, Ringert Rolf-Hermann, Seidlová-Wuttke Dana
Department of Urology, Institute of Human Genetics, Georg-August-University, Goettingen, Germany.
Carcinogenesis. 2005 Aug;26(8):1360-7. doi: 10.1093/carcin/bgi092. Epub 2005 Apr 21.
Isoflavones have been shown to exert antiproliferative effects on cancer cells by steroid receptor signaling. In this study, we demonstrate the potential of plant constituents extracted from Belamcanda chinensis as anticancer drugs, which regulate the aberrant expression of genes relevant in proliferation, invasion, immortalization and apoptosis. LNCaP cells were treated with B.chinensis extract, tectorigenin or other isoflavones and mRNA expression was quantified by using real time RT-PCR. In addition, ELISA, TRAP assays and western blots were used to measure protein expression or activity. Male nude mice (n=18) were injected subcutaneously with LNCaP cells and were fed with extracts from B.chinensis, and tumor development was monitored versus a control animal group (n=18). Tectorigenin and several other phytochemicals downregulated PDEF, PSA and IGF-1 receptor mRNA expression in vitro. Furthermore, PSA secretion and IGF-1 receptor protein expression were diminished, and hTERT mRNA expression and telomerase activity decreased after tectorigenin treatments. However, TIMP-3 mRNA was upregulated on tectorigenin treatment. Growth of subcutaneous tumors in nude mice was delayed and diminished in animals fed with extracts from B.chinensis. The downregulation of PDEF, PSA, hTERT and IGF-1 receptor gene expression by tectorigenin demonstrates the antiproliferative potential of these agents. The upregulation of TIMP-3 gene expression indicates a pro-apoptotic function of the drug and a reduction of the invasiveness of tumors. The animal experiments demonstrate that B.chinensis markedly inhibited the development of tumors in vivo. Thus, these compounds may be useful for the prevention or treatment of human prostate cancer.
异黄酮已被证明可通过类固醇受体信号传导对癌细胞发挥抗增殖作用。在本研究中，我们证明了从射干中提取的植物成分作为抗癌药物的潜力，这些成分可调节与增殖、侵袭、永生化和凋亡相关的基因的异常表达。用射干提取物、鸢尾黄素或其他异黄酮处理LNCaP细胞，并使用实时RT-PCR对mRNA表达进行定量。此外，采用ELISA、TRAP分析和蛋白质印迹法来测量蛋白质表达或活性。将雄性裸鼠（n = 18）皮下注射LNCaP细胞，并用射干提取物喂养，与对照动物组（n = 18）相比监测肿瘤发展情况。鸢尾黄素和其他几种植物化学物质在体外下调了PDEF、PSA和IGF-1受体mRNA的表达。此外，鸢尾黄素处理后，PSA分泌和IGF-1受体蛋白表达减少，hTERT mRNA表达和端粒酶活性降低。然而，鸢尾黄素处理后TIMP-3 mRNA上调。用射干提取物喂养的裸鼠皮下肿瘤生长延迟且缩小。鸢尾黄素对PDEF、PSA、hTERT和IGF-1受体基因表达的下调证明了这些药物的抗增殖潜力。TIMP-3基因表达的上调表明该药物具有促凋亡功能并降低了肿瘤的侵袭性。动物实验表明射干在体内显著抑制肿瘤发展。因此，这些化合物可能对预防或治疗人类前列腺癌有用。
