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Thelen, Paul
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Thelen, Paul
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Thelen, Paul
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Thelen, P.
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2005Journal Article [["dc.bibliographiccitation.firstpage","1360"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Carcinogenesis"],["dc.bibliographiccitation.lastpage","1367"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Scharf, Jens-Gerd"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Wuttke, Wolfgang"],["dc.contributor.author","Spengler, B."],["dc.contributor.author","Christoffel, V."],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.contributor.author","Seidlova-Wuttke, Dana"],["dc.date.accessioned","2018-11-07T10:56:59Z"],["dc.date.available","2018-11-07T10:56:59Z"],["dc.date.issued","2005"],["dc.description.abstract","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."],["dc.identifier.doi","10.1093/carcin/bgi092"],["dc.identifier.isi","000230724700006"],["dc.identifier.pmid","15845653"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50140"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0143-3334"],["dc.title","Tectorigenin and other phytochemicals extracted from leopard lily Belamcanda chinensis affect new and established targets for therapies in prostate cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2004Journal Article [["dc.bibliographiccitation.firstpage","1934"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","The Journal of Urology"],["dc.bibliographiccitation.lastpage","1938"],["dc.bibliographiccitation.volume","171"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Wuttke, Wolfgang"],["dc.contributor.author","Jarry, Hubertus"],["dc.contributor.author","Grzmil, M."],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.date.accessioned","2018-11-07T10:49:22Z"],["dc.date.available","2018-11-07T10:49:22Z"],["dc.date.issued","2004"],["dc.description.abstract","Purpose: The androgen sensitive prostate cancer cell line LNCaP is strongly positive for dihydrotestosterone (DHT) dependent telomerase activity, which is an important factor in cellular immortality and carcinogenesis. In this study we determined the potential of silibinin as an anticancer drug that down-regulates telomerase activity and prostate specific antigen (PSA) together with the co-activator of the androgen receptor prostate epithelium specific Ets transcription factor. Materials and Methods: LNCaP cells were treated with various concentrations of silibinin in the presence or absence of 5alpha-DHT. We used real-time reverse transcriptase-polymerase chain reaction to quantify mRNA expression of PSA, prostate epithelium specific Ets transcription factor and the catalytic subunit of telomerase vs the housekeeping gene porphobilinogen deaminase with gene specific, dual labeled fluorescence probes. PSA secretion from LNCaP cells in conditioned medium was measured with an Elecsys System 2010 (Roche Diagnostics, Mannheim, Germany) and telomerase activity in extracts from LNCaP cells was measured with a TRAP (telomeric repeat amplification protocol) assay. Results: Silibinin down-regulated PSA mRNA expression and PSA secretion in conditioned medium. Simultaneous stimulation with silibinin and 10(-8) M DHT also resulted in PSA down-regulation, whereas DHT alone increased PSA secretion. Telomerase catalytic subunit mRNA decreased significantly after silibinin stimulation. Telomerase activity was down-regulated by silibinin and stimulated by DHT. The 2 agents in combination resulted in telomerase down-regulation. Conclusions: The down-regulation of PSA by silibinin and its counteraction on DHT effects indicate that this compound can interact with the expression of genes that are regulated through the androgen receptor. Silibinin can also inhibit the telomerase activity that mediates cell immortality and carcinogenesis. The 2 effects underline the possible therapeutic use of silibinin as an antiproliferative agent in intervention for prostate cancer."],["dc.identifier.doi","10.1097/01.ju.0000121329.37206.1b"],["dc.identifier.isi","000220872800050"],["dc.identifier.pmid","15076315"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48411"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0022-5347"],["dc.title","Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2007Journal Article [["dc.bibliographiccitation.firstpage","199"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BJU International"],["dc.bibliographiccitation.lastpage","203"],["dc.bibliographiccitation.volume","100"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Peter, Thomas"],["dc.contributor.author","Huenermund, Anika"],["dc.contributor.author","Kaulfuss, Silke"],["dc.contributor.author","Seidlova-Wuttke, Dana"],["dc.contributor.author","Wuttke, Wolfgang"],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.contributor.author","Seseke, Florian"],["dc.date.accessioned","2018-11-07T11:00:51Z"],["dc.date.available","2018-11-07T11:00:51Z"],["dc.date.issued","2007"],["dc.description.abstract","To investigate the changes in expression underlying the marked reduction of tumour growth in vivo, by analysing the effect of Belamcanda chinensis extract (BCE) on LNCaP cells in vitro, as phytoestrogens are chemopreventive in prostate cancer, and in previous studies we examined the effects of the isoflavone tectorigenin isolated from B. chinensis on LNCaP prostate cancer cells, and a BCE consisting of 13 phytoestrogenic compounds on tumour-bearing nude mice. LNCaP cells were treated with 100, 400 or 1400 mu g/mL BCE; proliferation was assessed with an Alamar Blue assay. We used real-time reverse transcription-polymerase chain reaction to quantify mRNA expression of the androgen receptor (AR), the AR coactivator prostate derived Ets transcription factor (PDEF), NKX3.1, prostate specific antigen (PSA) and oestrogen receptor-beta (ER-beta) compared with the expression of the housekeeping gene porphobilinogen deaminase (PBGD). PSA secretion from LNCaP cells was measured and protein expression of the AR investigated by Western blot analysis. Concomitant with a marked decrease of tumour cell proliferation BCE down-regulated the expression of the AR, PDEF, NKX3.1 and PSA. In the same experiments, the expression of PBGD was unaltered, whereas ER-beta expression increased. Furthermore, AR protein and PSA secretion were markedly diminished after treatments with the BCE. BCE, comprising 13 different phytoestrogens, decreases the expression of the AR and its co-activator PDEF concomitant with diminished cell proliferation and PSA secretion. NKX3.1 expression was also reduced by BCE. We hypothesise that the positive effects of BCE are initiated by up-regulation of the ER-beta, a putative tumour-suppressor gene."],["dc.identifier.doi","10.1111/j.1464-410X.2007.06924.x"],["dc.identifier.isi","000247112400043"],["dc.identifier.pmid","17488304"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51023"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","1464-4096"],["dc.title","Phytoestrogens from Belamcanda chinensis regulate the expression of steroid receptors and related cofactors in LNCaP prostate cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2006Journal Article [["dc.bibliographiccitation.firstpage","521"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Planta Medica"],["dc.bibliographiccitation.lastpage","526"],["dc.bibliographiccitation.volume","72"],["dc.contributor.author","Seidlova-Wuttke, Dana"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Wuttke, Wolfgang"],["dc.date.accessioned","2018-11-07T09:56:31Z"],["dc.date.available","2018-11-07T09:56:31Z"],["dc.date.issued","2006"],["dc.description.abstract","The Cimicifuga racemosa extract BNO 1055 (CR) inhibits proliferation of human prostate cancer-derived LNCaP cells. Therefore, we tested the capability of this extract to inhibit formation and/or proliferation of tumors induced by subcutaneous (s.c.) inoculation of LNCaP cells in immunodeficient nu/nu mice. After inoculation of I million cells, 12 of 18 animals developed solid tumors while tumor development was seen in only 5 of 18 CR-treated animals and the size of the latter at termination of the experiments 10 weeks after inoculation was significantly smaller than in the control animals. Upon histological inspection, the amount of tumor tissue in the control animals was significantly larger than in the CR-treated animals while in the latter connective tissue was predominant. The CR treatment did not affect serum testosterone levels significantly regardless of whether the animals developed tumors or not. It is concluded that compounds in CR inhibit tumor development, proliferation and dignity of the tumors following s.c. inoculation of LNCaP cells. Hence, the CR extract may prove to be efficient in preventing and treatment of prostate cancer."],["dc.identifier.doi","10.1055/s-2006-931538"],["dc.identifier.isi","000238018100008"],["dc.identifier.pmid","16773536"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36968"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.relation.issn","0032-0943"],["dc.title","Inhibitory effects of a black cohosh (Cimicifuga racemosa) extract on prostate cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2007Journal Article [["dc.bibliographiccitation.firstpage","1271"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Der Urologe"],["dc.bibliographiccitation.lastpage","1274"],["dc.bibliographiccitation.volume","46"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Scharf, Jens-Gerd"],["dc.contributor.author","Wuttke, Wolfgang"],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.date.accessioned","2018-11-07T10:59:29Z"],["dc.date.available","2018-11-07T10:59:29Z"],["dc.date.issued","2007"],["dc.description.abstract","Prostate cancer is more frequently diagnosed in men from Western countries than from Asian societies. Therefore, nutritional factors such as phyto-oestrogens from soya are considered to cause this prostate cancer prevention effect. As there is no curative therapy for hormone-refractory prostate cancer, new strategies are in demand which might include phyto-oestrogens or inhibitors of histone deacetylases. Both approaches have in common the potential to reduce the aberrant androgen receptor and IGF receptor signalling. Furthermore, invasiveness and acquired survival strategies of turnours can be diminished. Reduced tumour cell proliferation and PSA secretion coincide with altered gene expression in the aforementioned processes. In addition, selective knock-down of genes by RNA interference afforded functional analyses regarding impact and succession of expression events involved in the beneficial effects caused by phyto-oestrogens and histone deacetylase inhibitors."],["dc.identifier.doi","10.1007/s00120-007-1452-0"],["dc.identifier.isi","000250342100104"],["dc.identifier.pmid","17641866"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50711"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","1433-0563"],["dc.title","Molecular principles of alternative treatment approaches for hormone-refractory prostate cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2006Conference Paper [["dc.bibliographiccitation.firstpage","S75"],["dc.bibliographiccitation.journal","Maturitas"],["dc.bibliographiccitation.lastpage","S82"],["dc.bibliographiccitation.volume","55"],["dc.contributor.author","Seidlova-Wuttke, Dana"],["dc.contributor.author","Pitzel, L."],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Wuttke, Wolfgang"],["dc.date.accessioned","2018-11-07T09:03:02Z"],["dc.date.available","2018-11-07T09:03:02Z"],["dc.date.issued","2006"],["dc.description.abstract","Objectives: Prostate cancers and many thereof derived cell lines, as the LNCaP cells, grow androgen-dependent. In vivo testosterone is locally converted by 5 alpha-reductase to 5 alpha-dihydrotestosterone (5 alpha-DHT) which is the major androgenic principle in prostates and seminal vesicles. The occurrence of prostate cancer and growth of LNCaP cells can be effectively inhibited by finasteride, a synthetic 5 alpha-reductase inhibitor and by a black cohosh (Cimicifuga racemosa, CR) extract. In the present contribution we tested whether the aqueous/ethanolic C. racemosa extract BNO 1055 contains 5u-reductase inhibitors. Methods: Immature 24-day-old mate rats were fed with testosterone (T)-containing food and injected with 30mg CR BNO 1055 or 0.5 mg finasteride for 5 days. Average daily T-uptake was 39 mg/animal. Other animals remained untreated or received vehicle injections only. Results: In comparison to totally untreated rats the testosterone treatment increased weight of prostates and seminal vesicles 3-5-fold and this proliferation was largely and equipotently inhibited by finasteride and CR BNO 1055. 5 alpha-Dihydrotestosterone concentrations in prostate tissue extracts were also reduced by both compounds and the testosterone-upregulated androgen receptor and insulin like growth factor I gene expression inhibited in the seminals vesicles. Conclusion: Taken together, these results indicate that the CR extract BNO 1055 contains one or more potent 5 alpha-reductase inhibitors which may make this extract suitable for the prevention and treatment of prostate cancer and possibly of benign prostate hyperplasia (BPH). (c) 2006 Elsevier Ireland Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.maturitas.2006.06.019"],["dc.identifier.isi","000242630700009"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24812"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Ireland Ltd"],["dc.publisher.place","Clare"],["dc.relation.conference","Symposium on Phytomedicines in Gynecology"],["dc.relation.eventlocation","Majorca, SPAIN"],["dc.relation.issn","0378-5122"],["dc.title","Inhibition of 5 alpha-reductase in the rat prostate by Cimicifuga racemosa"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI WOS2014Review [["dc.bibliographiccitation.firstpage","290"],["dc.bibliographiccitation.journal","The Journal of Steroid Biochemistry and Molecular Biology"],["dc.bibliographiccitation.lastpage","293"],["dc.bibliographiccitation.volume","139"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Wuttke, Wolfgang"],["dc.contributor.author","Seidlova-Wuttke, Dana"],["dc.date.accessioned","2018-11-07T09:46:54Z"],["dc.date.available","2018-11-07T09:46:54Z"],["dc.date.issued","2014"],["dc.description.abstract","Prostate cancer is the leading cause of cancer death in men of the Western world. A castration-resistant prostate cancer (CRPC) eventually will arise when a local restricted prostate carcinoma was not cured duly by radical prostatectomy or radiation therapy. Although androgen ablation therapies are considered the gold standard for treatments of advanced prostate cancer there is no curative therapy available at present. In previous pre-clinical and clinical trials several phytoestrogens were investigated for their anticancer potential in various models for prostate cancer. Phytoestrogens feature tumour preventive characteristics and most probably are involved in the low incidence rate of hormone related cancers in Asian countries. Phytoestrogens such as isoflavones can have a marked impact on the most essential therapy target of CRPC i.e. the androgen receptor. Furthermore, functional analyses solidified the notion of such drugs as androgen antagonistic. Phytoestrogens commonly feature low toxicity combined with a potential of targeted therapy. Thus, these drugs qualify for conceivable implementation in prostate cancer patients under active surveillance. In addition, relapse prevention with these drugs after radical prostatectomy or radiation therapy might be considered. This article is part of a Special Issue entitled 'Phytoestrogens'. (C) 2013 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.jsbmb.2013.06.009"],["dc.identifier.isi","000329599300036"],["dc.identifier.pmid","23872207"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34992"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0960-0760"],["dc.title","Phytoestrogens selective for the estrogen receptor beta exert anti-androgenic effects in castration resistant prostate cancer"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2004Journal Article [["dc.bibliographiccitation.firstpage","392"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Phytomedicine"],["dc.bibliographiccitation.lastpage","403"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Seidlova-Wuttke, Dana"],["dc.contributor.author","Hesse, O."],["dc.contributor.author","Jarry, Hubertus"],["dc.contributor.author","Rimoldi, G."],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Christoffel, V."],["dc.contributor.author","Wuttke, Wolfgang"],["dc.date.accessioned","2018-11-07T10:47:55Z"],["dc.date.available","2018-11-07T10:47:55Z"],["dc.date.issued","2004"],["dc.description.abstract","Belamcanda chinensis (BC) belongs to the family of iridaceae and the isoflavone tectorigenin has been isolated from the rhizome of this plant. Whether this isoflavone has estrogenic, possibly selective estrogen receptor modulator activities and if so, whether they are mediated via the estrogen receptor alpha or beta is unknown at present. Therefore, we performed binding studies with recombinant human ERalpha and ERbeta to show that tectorigenin binds to both receptor subtypes. In ERalpha-expressing MCF7 and ERbeta-expressing MDA-MB231 reporter gene transfected cells tectorigenin causes transactivation. When given intravenously to ovariectomized (ovx) rats, it inhibits pulsatile pituitary LH secretion. In postmenopausal women estrogen-unopposed LH pulses correlate with hot flushes. Therefore, suppression of pulsatile LH secretion may be beneficial in women suffering from hot flushes. Upon chronic application to ovx rats a BC extract containing 5% Belamcanda at a daily dose of 33 mg or 130 mg of the extract had no effect on uterine weight or on estrogen-regulated uterine gene expression while estrogenic effects in the bone, on bone mineral density of the metaphysis of the tibia could be established. Hence, tectorigenin may have antiosteoporotic effects also in postmenopausal women. Immunohistochemical staining of proliferating cell nuclear antigen-a proliferation marker-in the mammary gland did not indicate a mammotrophic effect of the tectorigenin-containing BC extract at both tested doses. In summary, tectorigenin or the R chinensis extract containing tectorigenin had a strong hypothalamotropic and osteotropic effect but no effect in the uterus or the mammary gland. Therefore, tectorigenin may be in the future a clinically useful selective estrogen receptor modulator. (C) 2004 Elsevier GmbH. All rights reserved."],["dc.identifier.doi","10.1016/j.phymed.2004.01.003"],["dc.identifier.isi","000223501600003"],["dc.identifier.pmid","15330494"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48077"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Urban & Fischer Verlag"],["dc.relation.issn","0944-7113"],["dc.title","Belamcanda chinensis and the thereof purified tectorigenin have selective estrogen receptor modulator activities"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2004Journal Article [["dc.bibliographiccitation.firstpage","25"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","International Journal of Oncology"],["dc.bibliographiccitation.lastpage","31"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Wuttke, Wolfgang"],["dc.contributor.author","Seseke, Florian"],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.date.accessioned","2018-11-07T10:52:41Z"],["dc.date.available","2018-11-07T10:52:41Z"],["dc.date.issued","2004"],["dc.description.abstract","Pathogenesis of prostate cancer is paralleled by aberrant transcriptional regulation which involves gene silencing by histone deacetylases. In cancer cells, inhibitors of histone deacetylases such as valproic acid can act as differentiation agents which relieve pro-apoptotic factors from transcriptional repression. We investigated the potential of the well-tolerated anticonvulsant valproic acid in prostate cancer cell line LNCaP and analyzed the activation of proapoptotic factors and resulting apoptosis. We used real time RT-PCR to quantify the mRNA expression of prostate-specific antigen, prostate-derived Ets transcription factor, tissue inhibitor of matrix metalloproteinase-3 and insulin-like growth factor binding protein-3. An automated sandwich-ELISA was used to measure secretion of prostate-specific antigen in conditioned cell culture media of LNCaP prostate cancer cells. Apoptotic cells were detected cytochemically and by applying immunocytochemistry. Activity of histone deacetylases in nuclear extracts was measured with a colorimetric assay kit. Valproic acid treatment caused a marked inhibition of histone deacetylases activity. Expression of prostate-derived Ets transcription factor and consequently prostate-specific antigen were down-regulated to basal levels in LNCaP cells. Pro-apoptotic factor caspase-3, tissue inhibitor of matrix metalloproteinase-3 and insulin-like growth factor binding protein-3 were up-regulated resulting in apoptosis of tumor cells. Valproic acid mediates marked effects on the expression of genes relevant in proliferation and apoptosis. Our study provides strong evidence that prostate cancer may benefit particularly from anti-proliferative stimuli from this well established drug."],["dc.identifier.isi","000187359500003"],["dc.identifier.pmid","14654937"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49170"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Professor D A Spandidos"],["dc.relation.issn","1019-6439"],["dc.title","Expressional changes after histone deacetylase inhibition by valproic acid in LNCaP human prostate cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details PMID PMC WOS2006Journal Article [["dc.bibliographiccitation.firstpage","195"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Der Urologe"],["dc.bibliographiccitation.lastpage","201"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Seseke, Florian"],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.contributor.author","Wuttke, Wolfgang"],["dc.contributor.author","Seidlova-Wuttke, Dana"],["dc.date.accessioned","2018-11-07T10:25:26Z"],["dc.date.available","2018-11-07T10:25:26Z"],["dc.date.issued","2006"],["dc.description.abstract","Introduction. Phytoestrogenes are plant-derived compounds that have been shown to exert an antiproliferative potential on prostate cancer cells, although the exact mechanisms are still unclear. In prostate cancer cells proliferation is regulated by modulation of the IGF-1 receptor (IGF-R-1) by the androgen receptor (AR) and its coactivator prostate derived El's factor (PDEF). Phytooestrogenes interact with these mechanisms as demonstrated exemplarily in the presented study with the isoflavone tectorigenin derived from Belamcanda chinensis. Material and methods. Cultured androgen-sensitive LNCaP prostate cancer cells were treated with tectorigenin of 100 mu M for 24 hours. The mRNA expression of AR, PSA, PDEF, hTERT, TIMP-3 and IGF-R-1 were quantified by real-time RT-PCR. Furthermore, the expression or activity of PSA, telomerase and IGF-R-1 was measured on the protein level. In addition, we investigated in nude mice the influence of a diet of extracts of Belamcanda chinensis on the growth of subcutaneously injected LNCaP cells versus a control group of animals fed with a soy-free diet. Results. In cultured LNCaP cells treatment with tectorigenin resulted in a significant down-regulation of the gene expression of AR, PDEF, PSA, IGF-R-1 and hTERT. On the protein level PSA secretion and the activity of telomerase and IGF-R-1 expression was also decreased. The gene expression of TIMP-3 was distinctly up-regulated by tectorigenin. Nude mice fed with Belamcanda chinensis extract showed a significantly de-creased incidence and tumor growth compared to controls. Conclusions. Tectorigenin shows an inhibition of the IGF-1-R modulated cell proliferation of PCa-Cells, due to modulation of the activity the co-activator PDEF independently from the AR. Furthermore, tectorigenin has pro-apoptotic effects and decreases tissue invasion by up-regulation of TIMP-3. Therefore, phytooestrogenes are an interesting option in the therapy of prostate especially advanced prostate cancer."],["dc.identifier.doi","10.1007/s00120-005-0932-3"],["dc.identifier.isi","000236017600007"],["dc.identifier.pmid","16237540"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42858"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","1433-0563"],["dc.title","Pharmacological potential of phytoestrogens in the treatment of prostate cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS