Carcinogenesis Advance Access published online on April 21, 2005
Carcinogenesis, doi:10.1093/carcin/bgi092
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1 Department of Urology, Georg-August-University, 37099 Göttingen, Germany
* To whom correspondence should be addressed. Isoflavones have been shown to exert antiproliferatve effects on cancer cells by steroid receptor signaling. In this study we demonstrate the potential of phytochemicals extracted from Belamcanda chinensis as anti-cancer drugs which regulate the aberrant expression of genes relevant in proliferation, invasion, immortalization and apoptosis. LNCaP cells were treated with Belamcanda 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 Belamcanda chinensis and tumor development was monitored versus a control animal group (n=18). Tectorigenin and several other phytochemicals down-regulated 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 up-regulated upon tectorigenin treatment. Growth of subcutaneous tumors in nude mice was delayed and diminished in animals fed with extracts from Belamcanda chinensis. The down-regulation of PDEF, PSA, hTERT and IGF-1 receptor gene expression by tectorigenin demonstrates the anti-proliferative potential of these agents. The up-regulation of TIMP-3 gene expression indicates a proapoptotic function of the drug and a reduction of the invasiveness of tumors. The animal experiments demonstrate that Belamcanda chinensis markedly inhibited the development of tumors in vivo. Thus, these compounds may be useful for the prevention or treatment of human prostate cancer.
Received November 9, 2004
Revised March 7, 2005
Accepted April 10, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Tectorigenin and other phytochemicals extracted from leopard lily Belamcanda chinensis affect new and established targets for therapies in prostate cancer
2 Department of Gastroenterology and Endocrinology, Georg-August-University, 37099 Göttingen, Germany
3 Institute of Human Genetics, Georg-August-University, 37099 Göttingen, Germany
4 Department of Pathology, Georg-August-University, 37099 Göttingen, Germany
5 Department of Clinical and Experimental Endocrinology, Georg-August-University, 37099 Göttingen, Germany
Paul Thelen, E-mail: pthelen{at}gwdg.de
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