{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T21:09:09Z","timestamp":1766869749053,"version":"build-2065373602"},"reference-count":93,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology (FCT), Portugal","award":["PTDC\/MED-ONC\/29402\/2017","UIDB\/04138\/2020","UIDP\/04138\/2020","SFRH\/BD\/145522\/2019","2020.07115.BD"],"award-info":[{"award-number":["PTDC\/MED-ONC\/29402\/2017","UIDB\/04138\/2020","UIDP\/04138\/2020","SFRH\/BD\/145522\/2019","2020.07115.BD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Among breast cancer (BC) patients, 15\u201325% develop BC brain metastases (BCBM), a severe condition due to the limited therapeutic options, which points to the need for preventive strategies. We aimed to find a drug able to boost blood\u2013brain barrier (BBB) properties and prevent BC cells (BCCs) extravasation, among PI3K, HSP90, and EGFR inhibitors and approved drugs. We used BCCs (4T1) and BBB endothelial cells (b.End5) to identify molecules with toxicity to 4T1 cells and safe for b.End5 cells. Moreover, we used those cells in mixed cultures to perform a high-throughput microscopy screening of drugs\u2019 ability to ameliorate BBB properties and prevent BCCs adhesion and migration across the endothelium, as well as to analyse miRNAs expression and release profiles. KW-2478, buparlisib, and minocycline hydrochloride (MH) promoted maximal expression of the junctional protein \u03b2-catenin and induced 4T1 cells nucleus changes. Buparlisib and MH further decreased 4T1 adhesion. MH was the most promising in preventing 4T1 migration and BBB disruption, tumour and endothelial cytoskeleton-associated proteins modifications, and miRNA deregulation. Our data revealed MH\u2019s ability to improve BBB properties, while compromising BCCs viability and interaction with BBB endothelial cells, besides restoring miRNAs\u2019 homeostasis, paving the way for MH repurposing for BCBM prevention.<\/jats:p>","DOI":"10.3390\/biomedicines10081988","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T23:44:25Z","timestamp":1660693465000},"page":"1988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Drug Screening Reveals Minocycline Hydrochloride as a Therapeutic Option to Prevent Breast Cancer Cells Extravasation across the Blood\u2013Brain Barrier"],"prefix":"10.3390","volume":"10","author":[{"given":"Joana","family":"Godinho-Pereira","sequence":"first","affiliation":[{"name":"iMed\u2014Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"given":"Margarida Dion\u00edsio","family":"Lopes","sequence":"additional","affiliation":[{"name":"iMed\u2014Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"given":"Ana Rita","family":"Garcia","sequence":"additional","affiliation":[{"name":"iMed\u2014Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4208-1086","authenticated-orcid":false,"given":"Hugo M.","family":"Botelho","sequence":"additional","affiliation":[{"name":"BioISI\u2014Biosystems and Integrative Sciences Institute, Faculty of Sciences, Universidade de Lisboa, Campo Grande, 1746-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5287-869X","authenticated-orcid":false,"given":"Rui","family":"Malh\u00f3","sequence":"additional","affiliation":[{"name":"BioISI\u2014Biosystems and Integrative Sciences Institute, Faculty of Sciences, Universidade de Lisboa, Campo Grande, 1746-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4639-6883","authenticated-orcid":false,"given":"In\u00eas","family":"Figueira","sequence":"additional","affiliation":[{"name":"iMed\u2014Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"},{"name":"Farm-ID\u2014Faculty of Pharmacy Association for Research and Development, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8493-4649","authenticated-orcid":false,"given":"Maria Alexandra","family":"Brito","sequence":"additional","affiliation":[{"name":"iMed\u2014Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. 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