{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:24:27Z","timestamp":1775150667106,"version":"3.50.1"},"reference-count":67,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER\u2014Fundo Europeu de Desenvolvimento Regional funds","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Gastric cancer (GC) ranked as the fifth most incident cancer in 2020 and the third leading cause of cancer mortality. Surgical prevention and radio\/chemotherapy are the main approaches used in GC treatment, and there is an urgent need to explore and discover innovative and effective drugs to better treat this disease. A new strategy arises with the use of repurposed drugs. Drug repurposing coupled with drug combination schemes has been gaining interest in the scientific community. The main objective of this project was to evaluate the therapeutic effects of alternative drugs in GC. For that, three GC cell lines (AGS, MKN28, and MKN45) were used and characterized. Cell viability assays were performed with the reference drug 5-fluororacil (5-FU) and three repurposed drugs: natamycin, nitazoxanide, and benztropine. Nitazoxanide displayed the best results, being active in all GC cells. Further, 5-FU and nitazoxanide in combination were tested in MKN28 GC cells, and the results obtained showed that nitazoxanide alone was the most promising drug for GC therapy. This work demonstrated that the repurposing of drugs as single agents has the ability to decrease GC cell viability in a concentration-dependent manner.<\/jats:p>","DOI":"10.3390\/biomedicines11030799","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T02:30:45Z","timestamp":1678156245000},"page":"799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5370-9586","authenticated-orcid":false,"given":"Eduarda","family":"Ribeiro","sequence":"first","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Departamento de Patologia e Imunologia Molecular, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Diana","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Departamento de Patologia e Imunologia Molecular, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8202-1459","authenticated-orcid":false,"given":"Mariana","family":"Pereira","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Departamento de Patologia e Imunologia Molecular, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8168-2415","authenticated-orcid":false,"given":"Bruna","family":"Lopes","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednicas Veterin\u00e1rias, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Centro de Estudos de Ci\u00eancia Animal (CECA), Instituto de Ci\u00eancias, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2531-3196","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednicas Veterin\u00e1rias, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Centro de Estudos de Ci\u00eancia Animal (CECA), Instituto de Ci\u00eancias, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8800-2195","authenticated-orcid":false,"given":"Ana Catarina","family":"Sousa","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednicas Veterin\u00e1rias, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Centro de Estudos de Ci\u00eancia Animal (CECA), Instituto de Ci\u00eancias, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"}]},{"given":"Andr\u00e9","family":"Coelho","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednicas Veterin\u00e1rias, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Centro de Estudos de Ci\u00eancia Animal (CECA), Instituto de Ci\u00eancias, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. 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Manuel II, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-6377","authenticated-orcid":false,"given":"Rui","family":"Alvites","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednicas Veterin\u00e1rias, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Centro de Estudos de Ci\u00eancia Animal (CECA), Instituto de Ci\u00eancias, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-3696","authenticated-orcid":false,"given":"F\u00e1tima","family":"Faria","sequence":"additional","affiliation":[{"name":"Departamento de Patologia e Imunologia Molecular, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0556-406X","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Citogen\u00e9tica, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4281-5438","authenticated-orcid":false,"given":"Beatriz","family":"Porto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Citogen\u00e9tica, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-9363","authenticated-orcid":false,"given":"Ana Colette","family":"Maur\u00edcio","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednicas Veterin\u00e1rias, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Centro de Estudos de Ci\u00eancia Animal (CECA), Instituto de Ci\u00eancias, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-1631","authenticated-orcid":false,"given":"Irina","family":"Amorim","sequence":"additional","affiliation":[{"name":"Departamento de Patologia e Imunologia Molecular, ICBAS\u2014School of Medicine and Biomedical Sciences\u2014University of Porto (UP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/vco.12249","article-title":"Gastric carcinoma in canines and humans, a review","volume":"15","author":"Hugen","year":"2017","journal-title":"Vet. 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