{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:25:36Z","timestamp":1785446736522,"version":"3.56.0"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec029\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Objective of the study was to evaluate the therapeutic potential of selenium nanoparticles (SeNPs) in combination with flutamide for treating prostate cancer (PCa) cell lines. The goal was to reduce the dosage of flutamide to decrease its side effects, especially hepatotoxicity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec030\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>PC3, LnCAP, and DU145 cell lines were treated with varying concentrations of SeNPs and Flutamide to determine IC50 values using the MTT assay. Subsequently, the IC50 concentration of flutamide was reduced by 50% and different concentrations of SeNPs were added to determine new IC50 concentrations of the combinations. Annexin-V\/ PI staining was performed to assess the apoptosis rate. The DNA cell cycle was analyzed using the PI staining technique. Migration, proliferative capability, and nucleus morphology of the cells were evaluated through the scratch-wound assay, colony-forming assay, and Hoechst staining, respectively. The expression of <jats:italic>SNAIL<\/jats:italic>, <jats:italic>KLK3<\/jats:italic>, <jats:italic>E-cadherin<\/jats:italic>, <jats:italic>VEGF-C<\/jats:italic>, <jats:italic>HIF-1\u03b1<\/jats:italic>, <jats:italic>Bcl2<\/jats:italic>, and <jats:italic>BAX<\/jats:italic> were examined using real-time PCR.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec031\">\n<jats:title>Results<\/jats:title>\n<jats:p>All treated groups significantly increased early and late apoptosis rate of the PCa cell lines, and induced SubG1\/G1 arrest in the cell cycle assay, compared to the control group. Significant inhibition of migration potential and colony formation was observed in all treated groups. Our results suggest that the combination group (50% decrease of Flutamide dosage) treatment upregulated apoptosis-related genes and <jats:italic>KLK3<\/jats:italic>, and downregulated genes involved in angiogenesis and proliferation similar to Flutamide alone (p &gt; 0.05).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec032\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>It is suggested that simultaneous administration of SeNPs and flutamide could potentially reduce the effective dosage of flutamide and decrease its adverse effects.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0318483","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T17:49:17Z","timestamp":1747676957000},"page":"e0318483","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Reducing the effective dosage of flutamide on prostate cancer cell lines through combination with selenium nanoparticles: An in-vitro study"],"prefix":"10.1371","volume":"20","author":[{"given":"Iman","family":"Menbari Oskouie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6311-1336","authenticated-orcid":true,"given":"Fatemeh","family":"Khatami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Shiralizadeh Dezfuli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahil","family":"Mashhadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akram","family":"Mirzaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyedeh Negin","family":"Hashemi Dougaheh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helia","family":"Azodian Ghajar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin","family":"Heshmat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1611-0362","authenticated-orcid":true,"given":"Seyed Mohammad Kazem","family":"Aghamir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"pone.0318483.ref001","first-page":"901578","article-title":"Translational bioinformatics for diagnostic and prognostic prediction of prostate cancer in the next-generation sequencing era","volume":"2013","author":"J Chen","year":"2013","journal-title":"Biomed Res Int"},{"issue":"3","key":"pone.0318483.ref002","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"11","key":"pone.0318483.ref003","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1158\/1055-9965.EPI-13-0568","article-title":"The heritability of prostate cancer in the Nordic Twin Study of Cancer","volume":"23","author":"JB Hjelmborg","year":"2014","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"6","key":"pone.0318483.ref004","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nrurol.2014.100","article-title":"The status of surgery in the management of high-risk prostate cancer","volume":"11","author":"C Bach","year":"2014","journal-title":"Nat Rev Urol"},{"issue":"2","key":"pone.0318483.ref005","first-page":"104","article-title":"Flutamide. 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