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The serine and threonine\u2013protein phosphatase 1 regulates key cellular processes and enhances androgen receptor activity in prostate cancer, even under castration-resistant conditions, suggesting a role in disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LNCaP and PC3 cells were treated with peptides mimicking protein phosphatase 1\u2013docking motifs in androgen receptor, alongside known bioportides (MSS1 and mitoparan). Cellular uptake was assessed by confocal microscopy and fluorescence assays. Viability was measured with PrestoBlue, and androgen receptor and Prostate-Specific Antigen expression was analyzed by quantitative reverse transcription\u2013polymerase chain reaction and Western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Androgen receptor sequence contains 3 protein phosphatase 1\u2013docking motifs: KVFF (binding site 1), HVVKW (binding site 2), and KPIYF (binding site 3). Binding site 1 and binding site 2 peptides were modified for better solubility, while binding site 3 was combined with the Tat sequence to enhance cellular uptake. Fluorophore-conjugated peptides successfully entered cells, with androgen receptor\u2013binding site 3 showing the highest internalization in LNCaP cells (P\u2009=\u2009.0495). Treatment with the 3 androgen receptor\u2013binding site peptides individually reduced cell viability in LNCaP and PC3 cells (P\u2009=\u2009.0352 and P\u2009=\u2009.0298, respectively). Combining androgen receptor\u2013binding site peptides statistically reduced cell viability, particularly with all 3 peptides together (LNCaP: 68%, P\u2009=\u2009.0369; PC3: 80%, P\u2009=\u2009.0369). No statistically significant changes in androgen receptor or prostate-specific antigen expression were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Bioportides targeting protein phosphatase 1\u2013docking motifs, especially when combined, decrease prostate cancer cell viability, and additional protein phosphatase 1\u2013interfering peptides such as MSS1 and mitoparan display potent cytotoxic effects. The absence of changes in androgen receptor and prostate-specific antigen expression highlights the need to further investigate their mechanisms of action.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jncics\/pkaf101","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T11:54:20Z","timestamp":1760097260000},"source":"Crossref","is-referenced-by-count":0,"title":["Exploring the feasibility of protein phosphatase 1\u2013docking motif-mimetic cell-penetrating peptides for modulating prostate carcinogenesis"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0384-3509","authenticated-orcid":false,"given":"Renato M","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Fardilha\u2019s Lab, Department of Medical Sciences, Institute of Biomedicine\u2014iBiMED, University of Aveiro , 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