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Beyond hormone dependence, extrinsic factors play a significant role in the risk of developing PCa, which raises concern about the influence of environmental compounds such as endocrine\u2010disrupting chemicals (EDCs). Tributyltin (TBT) is an EDC used in antifouling paints, and its androgenic (and obesogenic) actions have been described. This study investigated the effect of TBT on various cancer hallmarks, specifically its impact on the viability, metabolism, proliferation, migration, and invasion of prostate cells, using in\u00a0vitro and in\u00a0vivo models. Androgen\u2010sensitive (LNCaP) and androgen\u2010insensitive (PC3) PCa cells were exposed to 1\u2013100\u2009nM TBT for 24 and 48\u2009h. Additionally, LNCaP cells were treated with 100\u2009nM TBT in the presence of the androgen receptor antagonist bicalutamide (1\u201340\u2009\u03bcM) or 10\u2009nM TBT and\/or low\u2010density lipoprotein (LDL, 100\u2009\u03bcg\/mL) and 5\u03b1\u2010dihydrotestosterone (DHT, 10\u2009nM, 48\u2009h). Wistar rats were administered TBT (50\u2009\u03bcg\/kg) every 3\u2009days for 45\u2009days. TBT disrupted glycolytic flux and lipid handling in prostate cells, enhancing their proliferative activity. Moreover, 100\u2009nM TBT stimulated migration and invasion of LNCaP cells. Bicalutamide attenuated the effect of TBT in inducing glucose consumption and LNCaP cell proliferation. A 10\u00d7 lower TBT concentration maintained the stimulatory effects on LNCaP cells' viability, proliferation, and migration\/invasion, sustained by high LDL\u2010cholesterol availability and DHT. Our results show TBT as a potential inducer of PCa progression and aggressiveness and contribute to increasing awareness about the roles of EDCs in the prostate carcinogenic process.<\/jats:p>","DOI":"10.1002\/tox.70029","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:06:23Z","timestamp":1767697583000},"page":"709-729","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tributyltin Protumorigenic Effects Targeting Prostate Cancer Cell Metabolism, Proliferation, Migration, and Invasion"],"prefix":"10.1002","volume":"41","author":[{"given":"Mariana","family":"Feij\u00f3","sequence":"first","affiliation":[{"name":"RISE\u2010Health, Department of Chemistry, Faculty of Sciences University of Beira Interior  Covilh\u00e3 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00eds P.","family":"Br\u00e1s","sequence":"additional","affiliation":[{"name":"RISE\u2010Health, Department of Medical Sciences, Faculty of Health Sciences University of Beira Interior  Covilh\u00e3 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina M. D.","family":"Serra","sequence":"additional","affiliation":[{"name":"RISE\u2010Health, Department of Chemistry, Faculty of Sciences University of Beira Interior  Covilh\u00e3 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara R. S.","family":"Fonseca","sequence":"additional","affiliation":[{"name":"RISE\u2010Health, Department of Chemistry, Faculty of Sciences University of Beira Interior  Covilh\u00e3 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Correia","sequence":"additional","affiliation":[{"name":"RISE\u2010Health, Department of Medical Sciences, Faculty of Health Sciences University of Beira Interior  Covilh\u00e3 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno J.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences University of Beira Interior  Covilh\u00e3 Portugal"},{"name":"Instituto Portugu\u00eas de Oncologia de Coimbra Francisco Gentil  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana P.","family":"Duarte","sequence":"additional","affiliation":[{"name":"RISE\u2010Health, Department of Medical Sciences, Faculty of Health Sciences University of Beira Interior  Covilh\u00e3 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique J.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"RISE\u2010Health, Department of Medical Sciences, Faculty of Health Sciences University of Beira Interior  Covilh\u00e3 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1tia V.","family":"Vaz","sequence":"additional","affiliation":[{"name":"RISE\u2010Health, Department of Medical Sciences, Faculty of Health Sciences University of Beira Interior  Covilh\u00e3 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8181-488X","authenticated-orcid":false,"given":"S\u00edlvia","family":"Socorro","sequence":"additional","affiliation":[{"name":"RISE\u2010Health, Department of Medical Sciences, Faculty of Health Sciences University of Beira Interior  Covilh\u00e3 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2003.10.013"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0045(199604)28:4<251::AID-PROS6>3.0.CO;2-G"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(02)00413-5"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16166"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2015.06.009"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.87"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph182413047"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1059"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1129"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-15-0080"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801139-3.00002-8"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00178"},{"key":"e_1_2_11_14_1","unstructured":"Endocrine Society \u201cWhere We Stand on EDCs \u201daccessed September 16 2024 https:\/\/www.endocrine.org\/topics\/edc\/where\u2010we\u2010stand."},{"key":"e_1_2_11_15_1","first-page":"48","article-title":"New IMO Convention to Control Anti\u2010Fouling Systems on Ships","volume":"42","author":"Champ M.","year":"2001","journal-title":"Sea Technology"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.marenvres.2022.105689"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.02.011"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1205701"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2017.05.001"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2018.04.020"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.2000.9067"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2007.01.013"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287390802539061"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13679-017-0240-4"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21766"},{"issue":"4","key":"e_1_2_11_26_1","first-page":"1809","article-title":"LNCaP Model of Human Prostatic Carcinoma","volume":"43","author":"Horoszewicz J. 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