Tectorigenin and other phytochemicals extracted from leopard lily Belamcanda chinensis affect new and established targets for therapies in prostate cancer.
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.
Thelen
Paul
P
Department of Urology, Institute of Human Genetics, Georg-August-University, Goettingen, Germany. pthelen@gwdg.de
Scharf
Jens-Gerd
JG
Burfeind
Peter
P
Hemmerlein
Bernhard
B
Wuttke
Wolfgang
W
Spengler
Barbara
B
Christoffel
Volker
V
Ringert
Rolf-Hermann
RH
Seidlová-Wuttke
Dana
D
D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D007529:Isoflavones / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014183:Transplantation, Heterologous
D014408:Biomarkers, Tumor; D017931:DNA Primers; D007529:Isoflavones; D010936:Plant Extracts; C120039:tectorigenin