{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:31:52Z","timestamp":1784043112614,"version":"3.55.0"},"reference-count":76,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"WALA Heilmittel GmbH, Bad Boll, Germany"},{"name":"K\u00f6nig-Baudouin-Stiftung & Familie Harald G. M\u00fcller Fonds, Brussels, Belgium"},{"name":"Dr. Peter und Gabriele Strohmaier-Stiftung, G\u00fctersloh, Germany"},{"name":"Brigitta & Norbert Muth Stiftung, Wiesbaden, Germany"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Although multimodal therapeutic management has significantly improved outcome in prostate cancer (PCa) patients, treatment options for castrate-resistant disease remain challenging. Plant-derived mistletoe extracts have supported cancer patients and are, therefore, widely used as complementary medicine. However, mechanisms behind possible mistletoe benefits to PCa patients remain to be explored. The present study was designed to evaluate the effect of mistletoe extracts from four different host trees (Tiliae, Populi, Salicis, and Crataegi) on the growth and proliferation of PCa cell lines in vitro. PC3, DU145, and LNCaP cells were used to evaluate tumor cell growth (MTT assay) and proliferation (BrdU incorporation assay). Clonogenicity, apoptosis, cell cycle, and cell-cycle-regulating proteins (cyclin-dependent kinases (CDKs) and cyclins) were investigated, as was CD44 standard and splice variant expression and integrin \u03b1 and \u03b2 receptors. SiRNA knockdown studies were employed to investigate the functional relevance of integrins. All mistletoe extracts significantly inhibited cell growth in a dose-dependent manner and cell proliferation and clonogenicity were suppressed. Populi and Salicis induced cell-cycle arrest in the G2\/M phase and increased apoptosis. Both extracts down-regulated CDK1 and cyclin A and altered CD44 expression. Integrins \u03b15 in all cell lines and \u03b16 in DU145 and LNCaP were particularly diminished. Knocking down \u03b15 and \u03b16 induced cell growth inhibition in DU145. Mistletoe extracts block the growth and proliferation of PCa cells in vitro and therefore qualify for use in future animal studies to evaluate mistletoe as an adjunct to standard PCa treatment.<\/jats:p>","DOI":"10.3390\/cells14191535","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"1535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mistletoe Extracts Inhibit Progressive Growth of Prostate Cancer Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Sascha D.","family":"Markowitsch","sequence":"first","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Meiborg","sequence":"additional","affiliation":[{"name":"Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Rutz","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix K.-H.","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Haferkamp","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-8707","authenticated-orcid":false,"given":"Eva","family":"Juengel","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0129-7972","authenticated-orcid":false,"given":"Roman A.","family":"Blaheta","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"},{"name":"Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1053\/j.semnuclmed.2016.07.002","article-title":"Diagnostic and Therapeutic Strategies for Prostate Cancer","volume":"46","author":"Borre","year":"2016","journal-title":"Semin. 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