Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines

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...

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Main Authors: Eduarda Ribeiro, Diana Araújo, Mariana Pereira, Bruna Lopes, Patrícia Sousa, Ana Catarina Sousa, André Coelho, Alexandra Rêma, Rui Alvites, Fátima Faria, Cláudia Oliveira, Beatriz Porto, Ana Colette Maurício, Irina Amorim, Nuno Vale
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/11/3/799
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author Eduarda Ribeiro
Diana Araújo
Mariana Pereira
Bruna Lopes
Patrícia Sousa
Ana Catarina Sousa
André Coelho
Alexandra Rêma
Rui Alvites
Fátima Faria
Cláudia Oliveira
Beatriz Porto
Ana Colette Maurício
Irina Amorim
Nuno Vale
author_facet Eduarda Ribeiro
Diana Araújo
Mariana Pereira
Bruna Lopes
Patrícia Sousa
Ana Catarina Sousa
André Coelho
Alexandra Rêma
Rui Alvites
Fátima Faria
Cláudia Oliveira
Beatriz Porto
Ana Colette Maurício
Irina Amorim
Nuno Vale
author_sort Eduarda Ribeiro
collection DOAJ
description 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.
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spelling doaj.art-612d39c19b514ae684fdb305fd07f1902023-11-17T09:45:48ZengMDPI AGBiomedicines2227-90592023-03-0111379910.3390/biomedicines11030799Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell LinesEduarda Ribeiro0Diana Araújo1Mariana Pereira2Bruna Lopes3Patrícia Sousa4Ana Catarina Sousa5André Coelho6Alexandra Rêma7Rui Alvites8Fátima Faria9Cláudia Oliveira10Beatriz Porto11Ana Colette Maurício12Irina Amorim13Nuno Vale14OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, PortugalOncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, PortugalOncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, PortugalDepartamento de Clínicas Veterinárias, ICBAS—School of Medicine and Biomedical Sciences—University of Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, PortugalDepartamento de Clínicas Veterinárias, ICBAS—School of Medicine and Biomedical Sciences—University of Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, PortugalDepartamento de Clínicas Veterinárias, ICBAS—School of Medicine and Biomedical Sciences—University of Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, PortugalDepartamento de Clínicas Veterinárias, ICBAS—School of Medicine and Biomedical Sciences—University of Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, PortugalDepartamento de Clínicas Veterinárias, ICBAS—School of Medicine and Biomedical Sciences—University of Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, PortugalDepartamento de Clínicas Veterinárias, ICBAS—School of Medicine and Biomedical Sciences—University of Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, PortugalDepartamento de Patologia e Imunologia Molecular, ICBAS—School of Medicine and Biomedical Sciences—University of Porto (UP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, PortugalLaboratório de Citogenética, ICBAS—School of Medicine and Biomedical Sciences—University of Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, PortugalLaboratório de Citogenética, ICBAS—School of Medicine and Biomedical Sciences—University of Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, PortugalDepartamento de Clínicas Veterinárias, ICBAS—School of Medicine and Biomedical Sciences—University of Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, PortugalDepartamento de Patologia e Imunologia Molecular, ICBAS—School of Medicine and Biomedical Sciences—University of Porto (UP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, PortugalOncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, PortugalGastric 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.https://www.mdpi.com/2227-9059/11/3/799benztropinenatamycinnitazoxanidegastric cancerrepurposing drugs
spellingShingle Eduarda Ribeiro
Diana Araújo
Mariana Pereira
Bruna Lopes
Patrícia Sousa
Ana Catarina Sousa
André Coelho
Alexandra Rêma
Rui Alvites
Fátima Faria
Cláudia Oliveira
Beatriz Porto
Ana Colette Maurício
Irina Amorim
Nuno Vale
Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
Biomedicines
benztropine
natamycin
nitazoxanide
gastric cancer
repurposing drugs
title Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
title_full Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
title_fullStr Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
title_full_unstemmed Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
title_short Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
title_sort repurposing benztropine natamycin and nitazoxanide using drug combination and characterization of gastric cancer cell lines
topic benztropine
natamycin
nitazoxanide
gastric cancer
repurposing drugs
url https://www.mdpi.com/2227-9059/11/3/799
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