{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:19:14Z","timestamp":1787746754745,"version":"build-2784847793"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research","award":["20204YRYS5"],"award-info":[{"award-number":["20204YRYS5"]}]},{"DOI":"10.13039\/501100003852","name":"University of Campania \u201cLuigi Vanvitelli\u201d","doi-asserted-by":"publisher","award":["FSE+ 2021\/2027"],"award-info":[{"award-number":["FSE+ 2021\/2027"]}],"id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]},{"award":["FSE+ 2021\/2027"],"award-info":[{"award-number":["FSE+ 2021\/2027"]}],"id":[{"id":"https:\/\/ror.org\/02kqnpp86","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Nonylphenol (NP) is a chemical compound belonging to the class of alkylphenols (APs), known for its widespread environmental distribution and endocrine-disrupting properties. It is commonly used in the production of detergents, pesticides, and plastic materials and, owing to these properties, it can accumulate in both aquatic and terrestrial ecosystems. As a xenoestrogenic compound, NP can bind steroid receptors, including estrogen receptors (ERs), thereby activating ER-dependent pathways. In this work, we investigated the effects of NP alone and in combination with the endogenous hormones 17\u03b2-oestradiol (E2) and\/or testosterone (T) on a human non-tumoral prostate cell line (PNT1A). Cell viability and migration assays, together with analysis of ER expression and localization, were carried out to assess the xenoestrogenic activity of NP, particularly in the presence of E2 and T. Our results showed that NP retained its endocrine-disrupting features in the mixtures, positively affecting cell viability, except for the NP+E2 mixture, in which cell viability did not significantly differ from control, suggesting an antagonistic interaction between NP and E2. The mixtures also interfered with steroid receptor dynamics, affecting receptor expression and delaying receptor localization and activation kinetics. Moreover, all mixtures negatively affected cell migration compared with treatment with endogenous hormones alone. In conclusion, our results demonstrate that NP retains its xenoestrogenic behavior in mixture, inducing a significant alteration in prostate cell homeostasis.<\/jats:p>","DOI":"10.3390\/toxics14090755","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:59:23Z","timestamp":1787741963000},"page":"755","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Morpho-Functional Effects of Nonylphenol\u2013Steroid Hormone Co-Exposure on Human Prostate PNT1A Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1156-8107","authenticated-orcid":false,"given":"Aldo","family":"Mileo","sequence":"first","affiliation":[{"name":"Department of Life Science, Health and Health Professions, Link Campus University, Via del Casale di San Pio V 44, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7560-5692","authenticated-orcid":false,"given":"Teresa","family":"Chianese","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Cinthia 26, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5695-8225","authenticated-orcid":false,"given":"Stefania","family":"Boccia","sequence":"additional","affiliation":[{"name":"Department of Mental and Physical Health and Preventive Medicine, Section of Human Anatomy, University of Campania \u201cLuigi Vanvitelli\u201d, Largo Madonna delle Grazie 1, 80138 Naples, Italy"},{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Vico L. De Crecchio 7, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2609-4711","authenticated-orcid":false,"given":"Francesca","family":"Carrella","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, University of Sannio, Via F. de Sanctis snc, 82100 Benevento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8714-2717","authenticated-orcid":false,"given":"Benedetta","family":"Sgangarella Valvano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences \u201cVincenzo Tiberio\u201d, University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8844-3281","authenticated-orcid":false,"given":"Rosaria","family":"Sciarrillo","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, University of Sannio, Via F. de Sanctis snc, 82100 Benevento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2472-0435","authenticated-orcid":false,"given":"Luigi","family":"Rosati","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Cinthia 26, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0678-6329","authenticated-orcid":false,"given":"Lucia","family":"Capasso","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Vico L. De Crecchio 7, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3905-6154","authenticated-orcid":false,"given":"Antonio","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Mental and Physical Health and Preventive Medicine, Section of Human Anatomy, University of Campania \u201cLuigi Vanvitelli\u201d, Largo Madonna delle Grazie 1, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9044-2280","authenticated-orcid":false,"given":"Anna","family":"Capaldo","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Cinthia 26, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4617-8360","authenticated-orcid":false,"given":"Maria","family":"De Falco","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Cinthia 26, 80126 Naples, Italy"},{"name":"National Institute of Biostructures and Biosystems (INBB), 00136 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.toxlet.2011.07.032","article-title":"Recent trends in biomonitoring of bisphenol A, 4-t-octylphenol, and 4-nonylphenol","volume":"210","author":"Asimakopoulos","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_2","first-page":"520","article-title":"Removal of the Endocrine Disrupting Chemicals Nonylphenol from Water by Activated Carbon","volume":"178\u2013181","author":"Wang","year":"2012","journal-title":"Appl. Mech. Mater."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.envint.2013.10.006","article-title":"Environmental concentration of nonylphenol alters the development of urogenital and visceral organs in avian model","volume":"62","author":"Roig","year":"2014","journal-title":"Environ. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100616","DOI":"10.1016\/j.coesh.2025.100616","article-title":"Nonylphenol in agricultural soil system: Sources, effects, fate, and bioremediation strategies","volume":"45","author":"Cheng","year":"2025","journal-title":"Curr. Opin. Environ. Sci. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1002\/etc.5633","article-title":"Studies of Endocrine Disruptors: Nonylphenol and Isomers in Biological Models","volume":"42","year":"2023","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/j.1349-7006.2004.tb03223.x","article-title":"Possible enhancing effects of atrazine and nonylphenol on 7,12-dimethylbenz[a]anthracene-induced mammary tumor development in human c-Ha-ras proto-oncogene transgenic rats","volume":"95","author":"Fukamachi","year":"2004","journal-title":"Cancer Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1021\/acs.jafc.6b04916","article-title":"An Isomer-Specific Approach to Endocrine-Disrupting Nonylphenol in Infant Food","volume":"65","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10311-008-0143-4","article-title":"Kinetics of the oxidation of endocrine disruptor nonylphenol by ferrate(VI)","volume":"7","author":"Sharma","year":"2009","journal-title":"Environ. Chem. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Repkov\u00e1, A., Mi\u0161\u013eanov\u00e1, C., Hrab\u010d\u00e1kov\u00e1, J., Mas\u00e1r, M., Slez\u00e1kov\u00e1, Z., \u017demli\u010dka, L., and Valachovi\u010dov\u00e1, M. (2023). Relationship between Eating Habits and 4-Nonylphenol Concentration in Breast Milk of Women in Slovakia. Life, 13.","DOI":"10.3390\/life13122361"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1046\/j.1471-4159.2003.02270.x","article-title":"Nonylphenol induces the death of neural stem cells due to activation of the caspase cascade and regulation of the cell cycle","volume":"88","author":"Kudo","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/j.1365-2184.2011.00774.x","article-title":"Effects of 4-nonylphenol on proliferation of AGS gastric cells","volume":"44","author":"Manente","year":"2011","journal-title":"Cell Prolif."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/ddr.20355","article-title":"Nonylphenol-induced apoptotic pathways in SCM1 human gastric cancer cells","volume":"71","author":"Kuo","year":"2010","journal-title":"Drug Dev. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Park, H.-J., Zhang, M., Lee, W.-Y., Hong, K.-H., Do, J.T., Park, C., and Song, H. (2020). Toxic Effects of Nonylphenol on Neonatal Testicular Development in Mouse Organ Culture. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103491"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1080\/10934529.2012.680387","article-title":"The association between some endocrine disruptors and hypospadias in biological samples","volume":"47","author":"Choi","year":"2012","journal-title":"J. Environ. Sci. Health A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3892\/or.2021.7971","article-title":"Breast and prostate glands affected by environmental substances (Review)","volume":"45","author":"Bleak","year":"2021","journal-title":"Oncol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1002\/cncr.20408","article-title":"Human prostate cancer risk factors","volume":"101","author":"Bostwick","year":"2004","journal-title":"Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1159\/000457130","article-title":"HIV-Associated Urogenital Malignancies","volume":"40","author":"Hentrich","year":"2017","journal-title":"Oncol. Res. Treat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1056\/NEJMoa1503747","article-title":"Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer","volume":"373","author":"Sweeney","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_19","first-page":"408","article-title":"Breast cancer statistics, 2011","volume":"61","author":"DeSantis","year":"2011","journal-title":"CA Cancer J. Clin."},{"key":"ref_20","unstructured":"World Health Organization (2013). State of the Science of Endocrine Disrupting Chemicals\u20132012, World Health Organization."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ejca.2021.08.032","article-title":"A phase 2 randomized clinical trial of abiraterone plus ADT, apalutamide, or abiraterone and apalutamide in patients with advanced prostate cancer with non-castrate testosterone levels (LACOG 0415)","volume":"158","author":"Maluf","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.3390\/ijerph120404141","article-title":"Combined Effects of Nonylphenol and Bisphenol A on the Human Prostate Epithelial Cell Line RWPE-1","volume":"12","author":"Gan","year":"2015","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.tox.2016.05.024","article-title":"Nonylphenol effects on human prostate non-tumorigenic cells","volume":"357\u2013358","author":"Forte","year":"2016","journal-title":"Toxicology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.ecoenv.2019.05.035","article-title":"Nonylphenol acts on prostate adenocarcinoma cells via estrogen molecular pathways","volume":"180","author":"Forte","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.ecoenv.2017.09.030","article-title":"Interference of dibutylphthalate on human prostate cell viability","volume":"147","author":"Forte","year":"2018","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_26","unstructured":"Kortenkamp, A., Backhaus, T., and Faust, M. (2009). State of the Art Report on Mixture Toxicity, Final Report to the European Commission, Contract No. 070307\/2007\/485103\/ETU\/D.1."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1210\/me.2003-0335","article-title":"Characterization of the interactions of estrogen receptor and MNAR in the activation of cSrc","volume":"18","author":"Barletta","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chianese, T., Trinchese, G., Leandri, R., De Falco, M., Mollica, M.P., Scudiero, R., and Rosati, L. (2024). Glyphosate Exposure Induces Cytotoxicity, Mitochondrial Dysfunction and Activation of ER\u03b1 and ER\u03b2 Estrogen Receptors in Human Prostate PNT1A Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137039"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mileo, A., Chianese, T., Fasciolo, G., Venditti, P., Capaldo, A., Rosati, L., and De Falco, M. (2023). Effects of Dibutylphthalate and Steroid Hormone Mixture on Human Prostate Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814341"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s00253-009-2394-9","article-title":"Aerobic nonylphenol degradation and nitro-nonylphenol formation by microbial cultures from sediments","volume":"86","author":"Grotenhuis","year":"2010","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"93","DOI":"10.12717\/DR.2019.23.2.093","article-title":"Adverse Effect of Nonylphenol on the Reproductive System in F1 Male Mice: A Subchronic Low-Dose Exposure Model","volume":"23","author":"Kim","year":"2019","journal-title":"Dev. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Di Lorenzo, M., Mileo, A., Laforgia, V., De Falco, M., and Rosati, L. (2021). Alkylphenol Exposure Alters Steroidogenesis in Male Lizard Podarcis siculus. Animals, 11.","DOI":"10.3390\/ani11041003"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S1097-2765(03)00090-X","article-title":"Cyclic, Proteasome-Mediated Turnover of Unliganded and Liganded ER\u03b1 on Responsive Promoters Is an Integral Feature of Estrogen Signaling","volume":"11","author":"Reid","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"La Rosa, P., Pellegrini, M., Totta, P., Acconcia, F., and Marino, M. (2014). Xenoestrogens Alter Estrogen Receptor (ER) \u03b1 Intracellular Levels. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088961"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1210\/mend.14.8.0497","article-title":"Dynamics of Intracellular Movement and Nucleocytoplasmic Recycling of the Ligand-Activated Androgen Receptor in Living Cells","volume":"14","author":"Tyagi","year":"2000","journal-title":"Mol. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e2505797122","DOI":"10.1073\/pnas.2505797122","article-title":"The Role of Estrogen Receptor \u03b2 in Maintaining Basal Cells and Modulating the Immune Environment in the Prostate","volume":"122","author":"Wu","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1021\/acs.chemrestox.2c00180","article-title":"Nonylphenol Promoted Epithelial\u2013Mesenchymal Transition in Colorectal Cancer Cells by Upregulating the Expression of Regulator of Cell Cycle","volume":"35","author":"Zhang","year":"2022","journal-title":"Chem. Res. Toxicol."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/9\/755\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:25:44Z","timestamp":1787743544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/9\/755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["toxics14090755"],"URL":"https:\/\/doi.org\/10.3390\/toxics14090755","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}